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1

Cajigas, Sebastian, and Jahir Orozco. "Nanobioconjugates for Signal Amplification in Electrochemical Biosensing." Molecules 25, no. 15 (August 3, 2020): 3542. http://dx.doi.org/10.3390/molecules25153542.

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Nanobioconjugates are hybrid materials that result from the coalescence of biomolecules and nanomaterials. They have emerged as a strategy to amplify the signal response in the biosensor field with the potential to enhance the sensitivity and detection limits of analytical assays. This critical review collects a myriad of strategies for the development of nanobioconjugates based on the conjugation of proteins, antibodies, carbohydrates, and DNA/RNA with noble metals, quantum dots, carbon- and magnetic-based nanomaterials, polymers, and complexes. It first discusses nanobioconjugates assembly and characterization to focus on the strategies to amplify a biorecognition event in biosensing, including molecular-, enzymatic-, and electroactive complex-based approaches. It provides some examples, current challenges, and future perspectives of nanobioconjugates for the amplification of signals in electrochemical biosensing.
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Caizer, Costica, Isabela Simona Caizer, Roxana Racoviceanu, Claudia Geanina Watz, Marius Mioc, Cristina Adriana Dehelean, Tiberiu Bratu, and Codruța Soica. "Fe3O4-PAA–(HP-γ-CDs) Biocompatible Ferrimagnetic Nanoparticles for Increasing the Efficacy in Superparamagnetic Hyperthermia." Nanomaterials 12, no. 15 (July 27, 2022): 2577. http://dx.doi.org/10.3390/nano12152577.

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In this paper, we present the obtaining of Fe3O4-PAA–(HP-γ-CDs) ferrimagnetic nanobioconjugates (PAA: polyacrylic acid, HP-γ-CDs: hydroxypropyl gamma-cyclodextrins) in a hybrid core-shell biostructure (core: inorganic Fe3O4 nanoparticles, and shell: organic PAA–(HP-γ-CDs)) and their use in superparamagnetic hyperthermia without cellular toxicity and with increased efficacy for future alternative cancer therapy. In order to design the optimal experimental conditions for obtaining nanobioconjugates and then superparamagnetic hyperthermia (SPMHT), we used molecular docking simulation and computational assessment of the maximum specific loss power (SLP) that led to nanoparticles’ heating. The nanoparticles and nanobioconjugates obtained were studied and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transformed-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and magnetic measurements (MMs). The cell viability of the nanoparticles and nanobioconjugates was assessed by means of the MTT assay using human immortalized keratinocytes (HaCaT) as an in vitro model. Superparamagnetic hyperthermia with nanoparticles and nanobioconjugates was obtained experimentally in a magnetic field of 15.92 kA/m and frequency of 312.2 kHz for the magnetic nanoparticle core with a (average) diameter of 15.8 nm, which resulted in the maximum hyperthermic effect that led to a temperature of ~42.5 °C necessary in the therapy of tumors in a short time so as not to affect healthy tissues. The biological screening of Fe3O4-PAA nanoparticles and PAA–(HP-γ-CDs) nanobioconjugates showed no cytotoxic effect on HaCaT cells for a time interval of 24 h, both under standard (37 °C) and hyperthermia conditions (42.5 °C). Thus, Fe3O4-PA–(HP-γ-CDs) ferrimagnetic nanobioconjugates can be used successfully in superparamagnetic hyperthermia without toxicity and with increased efficiency due to the small layer thickness of the PAA–(HP-γ-CDs) shell, which is suitable in this alternative therapeutic technique.
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Umemura, Kazuo, and Shizuma Sato. "Scanning Techniques for Nanobioconjugates of Carbon Nanotubes." Scanning 2018 (June 13, 2018): 1–19. http://dx.doi.org/10.1155/2018/6254692.

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Nanobioconjugates using carbon nanotubes (CNTs) are attractive and promising hybrid materials. Various biological applications using the CNT nanobioconjugates, for example, drug delivery systems and nanobiosensors, have been proposed by many authors. Scanning techniques such as scanning electron microscopy (SEM) and scanning probe microscopy (SPM) have advantages to characterize the CNT nanobioconjugates under various conditions, for example, isolated conjugates, conjugates in thin films, and conjugates in living cells. In this review article, almost 300 papers are categorized based on types of CNT applications, and various scanning data are introduced to illuminate merits of scanning techniques.
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Asmat, Shamoon, Qayyum Husain, and Mohd Shoeb Khan. "A polypyrrole–methyl anthranilate functionalized worm-like titanium dioxide nanocomposite as an innovative tool for immobilization of lipase: preparation, activity, stability and molecular docking investigations." New Journal of Chemistry 42, no. 1 (2018): 91–102. http://dx.doi.org/10.1039/c7nj02951a.

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Prasad, Puja, and Shalini Gupta. "Nanobioconjugates: Weapons against Antibacterial Resistance." ACS Applied Bio Materials 3, no. 12 (November 20, 2020): 8271–85. http://dx.doi.org/10.1021/acsabm.0c01107.

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Sée, Violaine, Paul Free, Yann Cesbron, Paula Nativo, Umbreen Shaheen, Daniel J. Rigden, David G. Spiller, et al. "Cathepsin L Digestion of Nanobioconjugates upon Endocytosis." ACS Nano 3, no. 9 (September 3, 2009): 2461–68. http://dx.doi.org/10.1021/nn9006994.

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7

Ramírez-Acosta, Carlos M., Javier Cifuentes, Maria Claudia Castellanos, Rodolfo José Moreno, Carolina Muñoz-Camargo, Juan C. Cruz, and Luis H. Reyes. "PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation." Pharmaceutics 12, no. 6 (June 17, 2020): 561. http://dx.doi.org/10.3390/pharmaceutics12060561.

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Over the past decade, gene therapies have attracted much attention for the development of treatments for various conditions, including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here, we propose the development and in vitro evaluation of a nanostructured cell-penetrating vehicle based on core/shell, magnetite/silver nanoparticles. A subsequent conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. Additionally, the translocating peptide Buforin II was conjugated with the aid of a polyether amine polymer to facilitate translocation and endosome escape. The obtained nanobioconjugates (magnetite/silver-pDMAEMA-PEA-BUFII) were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS), and transmission electron microscopy (TEM). They were also encapsulated in lecithin liposomes to form magnetoliposomes. The cell viability of Vero cells in the presence of the nanobioconjugates was above 95% and declined to 80% for the magnetoliposomes. The hemolytic tendency of nanobioconjugates and magnetoliposomes was below 10%, while the platelet aggregation approached that of the negative control (i.e., 35%). Cytoplasm coverage values of about 50% for both Vero and neuroblastoma cells confirmed significant cell penetration. Pearson’s correlation coefficients for both cell lines allowed us to estimate 20–40% colocalization of the nanobioconjugates with lysotracker green, which implied high levels of endosomal escape. The developed vehicles were also capable of loading around 16% of the added DNA and releasing such cargo with 8% efficiency. The developed nanoplatform holds a significant promise to enable highly efficient gene therapies as it overcomes some of the major issues associated with their eventual translation to the pre-clinical and clinical scale.
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Cuellar, Monica, Javier Cifuentes, Jessica Perez, Alejandra Suarez-Arnedo, Julian Serna, Helena Groot, Carolina Muñoz-Camargo, and Juan Cruz. "Novel BUF2-magnetite nanobioconjugates with cell-penetrating abilities." International Journal of Nanomedicine Volume 13 (November 2018): 8087–94. http://dx.doi.org/10.2147/ijn.s188074.

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9

Giraldo, Kevin A., Juan Sebastian Bermudez, Carlos E. Torres, Luis H. Reyes, Johann F. Osma, and Juan C. Cruz. "Microfluidics for Multiphase Mixing and Liposomal Encapsulation of Nanobioconjugates: Passive vs. Acoustic Systems." Fluids 6, no. 9 (August 31, 2021): 309. http://dx.doi.org/10.3390/fluids6090309.

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One of the main routes to ensure that biomolecules or bioactive agents remain active as they are incorporated into products with applications in different industries is by their encapsulation. Liposomes are attractive platforms for encapsulation due to their ease of synthesis and manipulation and the potential to fuse with cell membranes when they are intended for drug delivery applications. We propose encapsulating our recently developed cell-penetrating nanobioconjugates based on magnetite interfaced with translocating proteins and peptides with the purpose of potentiating their cell internalization capabilities even further. To prepare the encapsulates (also known as magnetoliposomes (MLPs)), we introduced a low-cost microfluidic device equipped with a serpentine microchannel to favor the interaction between the liposomes and the nanobioconjugates. The encapsulation performance of the device, operated either passively or in the presence of ultrasound, was evaluated both in silico and experimentally. The in silico analysis was implemented through multiphysics simulations with the software COMSOL Multiphysics 5.5® (COMSOL Inc., Stockholm, Sweden) via both a Eulerian model and a transport of diluted species model. The encapsulation efficiency was determined experimentally, aided by spectrofluorimetry. Encapsulation efficiencies obtained experimentally and in silico approached 80% for the highest flow rate ratios (FRRs). Compared with the passive mixer, the in silico results of the device under acoustic waves led to higher discrepancies with respect to those obtained experimentally. This was attributed to the complexity of the process in such a situation. The obtained MLPs demonstrated successful encapsulation of the nanobioconjugates by both methods with a 36% reduction in size for the ones obtained in the presence of ultrasound. These findings suggest that the proposed serpentine micromixers are well suited to produce MLPs very efficiently and with homogeneous key physichochemical properties.
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Nazir, Samina, Tajammul Hussain, Salman Akbar Malik, and Ayesha Younus. "The Synthesis and Evaluation of Novel Lactate Dehydrogenase Nanobioconjugates." Current Nanoscience 8, no. 2 (March 1, 2012): 299–304. http://dx.doi.org/10.2174/157341312800167623.

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11

Narayanan, S. Shankara, and Samir Kumar Pal. "Structural and Functional Characterization of Luminescent Silver−Protein Nanobioconjugates." Journal of Physical Chemistry C 112, no. 13 (March 7, 2008): 4874–79. http://dx.doi.org/10.1021/jp709999x.

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12

Lyu, Yan, Chen Xie, Svetlana A. Chechetka, Eijiro Miyako, and Kanyi Pu. "Semiconducting Polymer Nanobioconjugates for Targeted Photothermal Activation of Neurons." Journal of the American Chemical Society 138, no. 29 (July 14, 2016): 9049–52. http://dx.doi.org/10.1021/jacs.6b05192.

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13

Caizer, Costica, Isabela Simona Caizer-Gaitan, Claudia Geanina Watz, Cristina Adriana Dehelean, Tiberiu Bratu, and Codruța Soica. "High Efficacy on the Death of Breast Cancer Cells Using SPMHT with Magnetite Cyclodextrins Nanobioconjugates." Pharmaceutics 15, no. 4 (April 4, 2023): 1145. http://dx.doi.org/10.3390/pharmaceutics15041145.

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In this study, we present the experimental results obtained in vitro on the human breast adenocarcinoma cell line (MCF-7) by applying superparamagnetic hyperthermia (SPMHT) using novel Fe3O4-PAA–(HP-γ-CDs) (PAA is polyacrylic acid and HP-γ-CDs is hydroxypropyl gamma-cyclodextrins) nanobioconjugates previously obtained by us. In the in vitro SPMHT experiments, we used concentrations of 1, 5 and 10 mg/mL of Fe3O4 ferrimagnetic nanoparticles from Fe3O4-PAA–(HP-γ-CDs) nanobioconjugates suspended in culture media containing 1 × 105 MCF-7 human breast adenocarcinoma cells. The harmonic alternating magnetic field used in the in vitro experiments that did not affect cell viability was found to be optimal in the range of 160–378 Gs and at a frequency of 312.2 kHz. The appropriate duration of the therapy was 30 min. After applying SPMHT with these nanobioconjugates under the above conditions, MCF-7 cancer cells died out in a very high percentage, of until 95.11%. Moreover, we studied the field up to which magnetic hyperthermia can be safely applied without cellular toxicity, and found a new upper biological limit H × f ~9.5 × 109 A/m⋅Hz (H is the amplitude and f is the frequency of the alternating magnetic field) to safely apply the magnetic field in vitro in the case of MCF-7 cells; the value was twice as high compared to the currently known value. This is a major advantage for magnetic hyperthermia in vitro and in vivo, because it allows one to achieve a therapy temperature of 43 °C safely in a much shorter time without affecting healthy cells. At the same time, using the new biological limit for a magnetic field, the concentration of magnetic nanoparticles in magnetic hyperthermia can be greatly reduced, obtaining the same hyperthermic effect, while at the same time, reducing cellular toxicity. This new limit of the magnetic field was tested by us in vitro with very good results, without the cell viability decreasing below ~90%.
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14

Galstyan, Anna, Dmytro Klymyshyn, Rameshwar Patil, Hui Ding, Ekaterina Shatalova, Eggehard Holler, Alexander Ljubimov, Keith Black, Tao Sun, and Julia Ljubimova. "TMIC-47. INHIBITION OF GLIOBLASTOMA GROWTH THROUGH TUMOR-MICROENVIRONMENT CROSSTALK USING CLINICALLY SUITABLE NANOBIOCONJUGATE." Neuro-Oncology 21, Supplement_6 (November 2019): vi258. http://dx.doi.org/10.1093/neuonc/noz175.1081.

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Abstract Tumor environment in glioblastoma (GBM) is a dynamic interactive complex between tumor, immune and stem cells and extracellular matrix (ECM). In 226 patient glioma samples, we found a clinical correlation between expression of tumor vascular laminin-411 (α4β1γ1) and cancer stem cell (CSC) markers: Notch pathway members, CD133, Nestin, and c-Myc, with faster tumor recurrence and shorter survival of patients (Tao S, et al, Cancer Res., 2019). Novel nanotechnology approach to block trimeric ECM laminin-411 was developed for GBM treatment in experimental and preclinical models on human U87MG and LN229, and patient-derived TS543 and TS576 GBM cell lines. Nanobioconjugates (NBC) based on natural polymer, poly(β-L-malic acid), with antisense against laminin-411 α4 and β-chains, endosome escape unit (Ding H, et al, PNAS, USA, 2010), antibodies for blood-brain barrier (BBB) crossing and tumor targeting was characterized for toxicity and biodistribution according to FDA guidelines. Ex vivo depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of intracranial tumors in mice, and significantly increased survival in hosts compared to mice with untreated cells. A nanobioconjugate potentially suitable for clinical use and capable of crossing BBB was designed to block laminin-411 expression. In biodistribution studies the NBC labeled with 125I on tyrosines of attached antibodies was accumulated in GBM but not in healthy brain tissue. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, Notch signaling system through the b1 integrin-Dll4 (Notch ligand) pathway. No toxicity revealed in 4 naïve Cynomolgus macaques after administration of three therapeutic 1X and acute 10X dosages of NBC. Conclusion: An efficient strategy of GBM treatment was developed via targeting a critical component of the tumor microenvironment, laminin-411, which is independent of heterogeneous genetic mutations in glioblastomas. Support: NIH grants U01CA151815, R01CA188743, R01CA206220, R01CA209921.
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Balu, Rajkamal, Jasmin Whittaker, Naba K. Dutta, Christopher M. Elvin, and Namita R. Choudhury. "Multi-responsive biomaterials and nanobioconjugates from resilin-like protein polymers." J. Mater. Chem. B 2, no. 36 (2014): 5936–47. http://dx.doi.org/10.1039/c4tb00726c.

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In this review, we highlight and discuss the design, synthesis, unique molecular architecture, advanced responsive behaviour and functionality of hydrogels, solid–liquid interfaces, nanoparticles and nano-biohybrids derived from resilin-mimetic protein polymers.
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Zimet, Patricia, Ruby Valadez, Sofía Raffaelli, María Belén Estevez, Helena Pardo, and Silvana Alborés. "Biogenic Silver Nanoparticles Conjugated with Nisin: Improving the Antimicrobial and Antibiofilm Properties of Nanomaterials." Chemistry 3, no. 4 (November 4, 2021): 1271–85. http://dx.doi.org/10.3390/chemistry3040092.

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Microbial technology offers a green alternative for the synthesis of value-added nanomaterials. In particular, fungal compounds can improve silver nanoparticle production, stabilizing colloidal nanoparticles. Based on a previous study by our group, silver nanoparticles obtained using the extracellular cell-free extracts of Phanerochaete chrysosporium (PchNPs) have shown antimicrobial and antibiofilm activity against Gram-negative bacteria. Moreover, nisin—a bacteriocin widely used as a natural food preservative—has recently gained much attention due its antimicrobial action against Gram-positive bacteria in biomedical applications. Therefore, the aim of this work was to conjugate biogenic silver nanoparticles (PchNPs) with nisin to obtain nanoconjugates (PchNPs@nis) with enhanced antimicrobial properties. Characterization assays were conducted to determine physicochemical properties of PchNPs@nis, and also their antibacterial and antibiofilm activities were studied. The formation of PchNPs@nis was confirmed by UV-Vis, TEM, and Raman spectroscopy analysis. Different PchNPs@nis nanobioconjugates showed diameter values in the range of 60–130 nm by DLS and surface charge values between −20 and −13 mV. Nisin showed an excellent affinity to PchNPs, with binding efficiencies higher than 75%. Stable synthesized PchNPs@nis nanobioconjugates were not only able to inhibit biofilm formation by S. aureus, but also showed inhibition of the planktonic cell growth of Staphyloccocus aureus and Escherichia coli, broadening the spectrum of action of the unconjugated antimicrobials against Gram-positive and Gram-negative bacteria. In conclusion, these results show the promising application of PchNPs@nis, prepared via green technology, as potential antimicrobial nanomaterials.
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Lopez-Barbosa, Natalia, Alejandra Suárez-Arnedo, Javier Cifuentes, Andres Fernando Gonzalez Barrios, Carlos A. Silvera Batista, Johann F. Osma, Carolina Muñoz-Camargo, and Juan C. Cruz. "Magnetite–OmpA Nanobioconjugates as Cell-Penetrating Vehicles with Endosomal Escape Abilities." ACS Biomaterials Science & Engineering 6, no. 1 (November 14, 2019): 415–24. http://dx.doi.org/10.1021/acsbiomaterials.9b01214.

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Cywinski, Piotr J., Tommy Hammann, Dominik Hühn, Wolfgang J. Parak, Niko Hildebrandt, and Hans-Gerd Löhmannsröben. "Europium-quantum dot nanobioconjugates as luminescent probes for time-gated biosensing." Journal of Biomedical Optics 19, no. 10 (July 2, 2014): 101506. http://dx.doi.org/10.1117/1.jbo.19.10.101506.

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Manan, Fatin Myra Abd, Ida Nurhazwani Abd Rahman, Nur Haziqah Che Marzuki, Naji A. Mahat, Fahrul Huyop, and Roswanira Abdul Wahab. "Statistical modelling of eugenol benzoate synthesis using Rhizomucor miehei lipase reinforced nanobioconjugates." Process Biochemistry 51, no. 2 (February 2016): 249–62. http://dx.doi.org/10.1016/j.procbio.2015.12.002.

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Singh, Rohini, and Shalini Gupta. "Dual functionality nanobioconjugates: a new tool for intracellular bacterial targeting in cancer cells?" Therapeutic Delivery 9, no. 5 (May 2018): 317–20. http://dx.doi.org/10.4155/tde-2018-0010.

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Ahmad, Razi, Abhijeet Mishra, and Meryam Sardar. "Peroxidase-TiO2 Nanobioconjugates for the Removal of Phenols and Dyes from Aqueous Solutions." Advanced Science, Engineering and Medicine 5, no. 10 (October 1, 2013): 1020–25. http://dx.doi.org/10.1166/asem.2013.1387.

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22

Khan, Shadab Ali, Sanjay Gambhir, and Absar Ahmad. "Extracellular biosynthesis of gadolinium oxide (Gd2O3) nanoparticles, their biodistribution and bioconjugation with the chemically modified anticancer drug taxol." Beilstein Journal of Nanotechnology 5 (March 7, 2014): 249–57. http://dx.doi.org/10.3762/bjnano.5.27.

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As a part of our programme to develop nanobioconjugates for the treatment of cancer, we first synthesized extracellular, protein-capped, highly stable and well-dispersed gadolinium oxide (Gd2O3) nanoparticles by using thermophilic fungus Humicola sp. The biodistribution of the nanoparticles in rats was checked by radiolabelling with Tc-99m. Finally, these nanoparticles were bioconjugated with the chemically modified anticancer drug taxol with the aim of characterizing the role of this bioconjugate in the treatment of cancer. The biosynthesized Gd2O3 nanoparticles were characterized by UV–vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoemission spectroscopy (XPS). The Gd2O3–taxol bioconjugate was confirmed by UV–vis spectroscopy and fluorescence microscopy and was purified by using high performance liquid chromatography (HPLC).
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Bencze, László Csaba, Judith H. Bartha-Vári, Gabriel Katona, Monica Ioana Toşa, Csaba Paizs, and Florin-Dan Irimie. "Nanobioconjugates of Candida antarctica lipase B and single-walled carbon nanotubes in biodiesel production." Bioresource Technology 200 (January 2016): 853–60. http://dx.doi.org/10.1016/j.biortech.2015.10.072.

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Verma, Pramod Kumar, Anupam Giri, Nguyen T. K. Thanh, Le Duc Tung, Oindrila Mondal, Mrinal Pal, and Samir Kumar Pal. "Superparamagnetic fluorescent nickel–enzyme nanobioconjugates: synthesis and characterization of a novel multifunctional biological probe." Journal of Materials Chemistry 20, no. 18 (2010): 3722. http://dx.doi.org/10.1039/b925477c.

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Sangtani, Ajmeeta, Eleonora Petryayeva, Miao Wu, Kimihiro Susumu, Eunkeu Oh, Alan L. Huston, Guillermo Lasarte-Aragones, Igor L. Medintz, W. Russ Algar, and James B. Delehanty. "Intracellularly Actuated Quantum Dot–Peptide–Doxorubicin Nanobioconjugates for Controlled Drug Delivery via the Endocytic Pathway." Bioconjugate Chemistry 29, no. 1 (December 21, 2017): 136–48. http://dx.doi.org/10.1021/acs.bioconjchem.7b00658.

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Mohamad, NurRoyhaila, Fahrul Huyop, Hassan Youssef Aboul-Enein, Naji Arafat Mahat, and Roswanira Abdul Wahab. "Response surface methodological approach for optimizing production of geranyl propionate catalysed by carbon nanotubes nanobioconjugates." Biotechnology & Biotechnological Equipment 29, no. 4 (April 18, 2015): 732–39. http://dx.doi.org/10.1080/13102818.2015.1034177.

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Perez, Jessica, Javier Rueda, Mónica Cuellar, Alejandra Suarez-Arnedo, Juan C. Cruz, and Carolina Muñoz-Camargo. "Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles." International Journal of Nanomedicine Volume 14 (October 2019): 8483–97. http://dx.doi.org/10.2147/ijn.s224286.

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Preethi, R., and P. R. Padma. "ANTICANCER ACTIVITY OF SILVER NANOBIOCONJUGATES SYNTHESISED FROM PIPER BETLE LEAVES EXTRACT AND ITS ACTIVE COMPOUND EUGENOL." International Journal of Pharmacy and Pharmaceutical Sciences 8, no. 9 (September 1, 2016): 201. http://dx.doi.org/10.22159/ijpps.2016.v8i9.12993.

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<p><strong>Objective: </strong>Our present study deals with the anticancer property of silver nano bio conjugates synthesized from the methanolic extract of <em>Piper betle</em> leaves and the pure compound eugenol.</p><p><strong>Methods: </strong>The anticancer activity of the nano bio conjugates synthesized from the extract and pure compound, in comparison with their respective non-conjugated raw material, were studied using cancer cell lines. The anticancer activity was analyzed by cell viability and staining techniques. The cell viability was determined by the MTT assay and the apoptosis was evaluated by the AO/EtBr staining method, which was carried out in both the cancerous (oral carcinoma (KB) cell lines) and non-cancerous cells (primary cultured human buccal cells). The phase of cell death was assessed by the flow cytometry followed by the cytotoxicity assessment.</p><p><strong>Results: </strong>The results revealed that <em>Piper</em> <em>betle</em> leaves as well as their active phenolic compound eugenol exhibited strong anticancer activity in KB oral carcinoma cells. The anticancer effect of the extract was attributable to the component phenolics, eugenol respectively in betel leaves, as the phenolics also exhibited strong cytotoxicity in cancer cells. The anticancer activity increased by a marked magnitude when the extract/compound was administered as nano-bio conjugates. The significant observation was the differential effect evoked by the AgNPs, which was non-toxic to non-cancerous buccal cells while evoking a strong cytotoxicity in the cancer cells.</p><p><strong>Conclusion: </strong>The results proved that the phytoconstituents like phenols in the betel leaves play a major role in the reduction of nano bio conjugates. The anticancer properties of silver nano bio conjugates were higher in the conjugated nanoform than the non-conjugated form.</p>
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Ljubimov, Vladimir, Rameshwar Patil, Eggehard Holler, Julia Ljubimova, and Keith Black. "NIMG-01. MRI VIRTUAL BIOPSY AND TREATMENT OF PRIMARY OR BRAIN METASTATIC TUMORS WITH TARGETED NANOBIOCONJUGATES." Neuro-Oncology 22, Supplement_2 (November 2020): ii146. http://dx.doi.org/10.1093/neuonc/noaa215.614.

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Abstract Differential diagnosis of brain magnetic resonance imaging (MRI) enhancement(s) remains a significant problem, which may be difficult to resolve without biopsy that can be often dangerous or even impossible. Such MRI enhancement(s) can result from metastasis of primary tumors such as lung or breast, radiation necrosis, infections or a new primary brain tumor (glioma, meningioma). Neurological symptoms are often the same on initial presentation. METHODS: We present a noninvasive tumor-specific imaging approach “MRI virtual biopsy” by engineering new nano imaging agents (NIA) on polymalic acid polymer (PMLA) scaffold containing linear-Gd-DOTA or star-Gd-DOTA moieties for differential diagnosis of brain tumors. The strategy is that after non-invasive MRI diagnosis recognizing the brain lesion on the basis of its molecular signatures, the primary cancer or brain metastasis (BM) is suppressed by tumor-specific molecular inhibitor(s), which is structurally similar to the used NIA. Anti-TfR antibody or Angiopep-2 (AP-2) peptide used to cross blood-brain barrier (BBB) by receptor-mediated transcytosis, and targeting antibody against EFGR- or HER2-overexpressing tumors were covalently attached to PMLA to recognize the tissues of interest. Delivery of contrast agents across BBB was studied by optical imaging. MRI signals in healthy brain and tumors were quantified using 9.4-Tesla MRI system. RESULTS: High specific signal values prevailed for 3 hours for NIA, in comparison with clinical Gd (MultiHance) that declined rapidly. In newly developed double tumor xenogeneic mouse models of brain metastasis this method allowed differential diagnosis of HER2- and EGFR-expressing brain tumors. After MRI diagnosis, breast and lung cancer brain metastases were successfully treated with similar tumor-targeted nanoconjugates carrying molecular inhibitors of EGFR or HER2 instead of imaging contrast agent. The treatment resulted in significant increase of animal survival and markedly reduced immunostaining for several cancer stem cell markers. Support: NIH grants: R01 CA188743, R01 CA206220, R01 CA209921
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Patil, Rameshwar, Alexander V. Ljubimov, Pallavi R. Gangalum, Hui Ding, Jose Portilla-Arias, Shawn Wagner, Satoshi Inoue, et al. "MRI Virtual Biopsy and Treatment of Brain Metastatic Tumors with Targeted Nanobioconjugates: Nanoclinic in the Brain." ACS Nano 9, no. 5 (May 6, 2015): 5594–608. http://dx.doi.org/10.1021/acsnano.5b01872.

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Kumar, Dheeraj, Navin Sakhare, Soumen Das, Pooja Kale, Anupam Mathur, Shubhangi Mirapurkar, Sheela Muralidharan, et al. "Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers." Nuclear Medicine and Biology 93 (February 2021): 1–10. http://dx.doi.org/10.1016/j.nucmedbio.2020.11.001.

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Mirkin, Chad A. "The Polyvalent Gold Nanoparticle Conjugate—Materials Synthesis, Biodiagnostics, and Intracellular Gene Regulation." MRS Bulletin 35, no. 7 (July 2010): 532–39. http://dx.doi.org/10.1557/mrs2010.602.

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AbstractAdvances in nanoscale directed assembly strategies have enabled researchers to analogize atomic assembly via chemical reactions and nanoparticle assembly, creating a new nanoscale “periodic table.” We are just beginning to realize the nanoparticle equivalents of molecules and extended materials and are currently developing the ground rules for creating programmable nanometer-scale coordination environments. The ability to create a diverse set of nanoscale architectures from one class of nanoparticle building blocks would allow for the synthesis of designer materials, wherein the physical properties of a material could be predicted and controlled a priori. Our group has taken the first steps toward this goal and developed a means of creating tailorable assembly environments using DNA-nanoparticle conjugates. These nanobioconjugates combine the discrete plasmon resonances of gold nanoparticles with the synthetically controllable and highly selective recognition properties of DNA. Herein, we elucidate the beneficial properties of these materials in diagnostic, therapeutic, and detection capabilities and project their potential use as nanoscale assembly agents to realize complex three-dimensional nanostructures.
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Ljubimov, Alexander V., Rameshwar Patil, Hui Ding, Liron Israel, Eggehard Holler, Julia Y. Ljubimova, Tao Sun, and Keith L. Black. "Abstract 575: Brain delivery of clinically suitable nanobioconjugates to inhibit glioblastoma growth through extracellular matrix-immune cell crosstalk." Cancer Research 83, no. 7_Supplement (April 4, 2023): 575. http://dx.doi.org/10.1158/1538-7445.am2023-575.

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Abstract Introduction: Tumor growth, invasion, and escape from immune surveillance largely depend on cancer microenvironment. Laminins are trimeric proteins and essential components of glioblastoma (GBM) microenvironment/extracellular matrix (ECM). In brain glioma samples from 230 patients, we found a correlation between the overexpression of tumor ECM protein laminin-411 (α4β1γ1) and faster tumor recurrence with shorter patient survival. Laminin-411 is produced by endothelial cells, neutrophils, monocytes, platelets, lymphocytes, and glioma cells and can modulate the immune system. Novel nanotechnology approach to block trimeric laminin-411 and activate of brain local immune system with brain delivery of PD-1 checkpoint inhibitor was developed for future translational application. Methods: Nanobioconjugates (NBC) based on poly (β-L-malic acid, P), were synthesized, characterized and used to intravenously treat mice with intracranial syngeneic GL261 or CT-2A GBM. The lead NBCs P/PEG/LLL(40%)/AON(α4β1)(2.0%)/AP-2(2%) and P/PEG/LLL(40%)/AP-2(2%)/αPD-1(0.2%) contained antisense to laminin-411 α4 and β1 chains, or αPD-1 antibody as well as trileucine (LLL) peptide for endosomal escape and AP-2 peptide for BBB crossing and tumor cell targeting. CRISPR/Cas9 constructs were used to knockdown α4 and β1 laminin chains in GBM ex vivo. Flow cytometry and RNA-seq analyses were performed to evaluate treatment. Results: Laminin-411 depletion with CRISPR/Cas9 and multifunctional NBC in vivo treatment equally suppressed GBM growth and significantly prolonged animal survival. The brain privileged immune system was activated upon treatment with a significant increase of CD3+, CD8+ T cells, NK, IFNγ+ NK cells, and M1 macrophages. RNA-sec analyses after treatment with a combination of NBC suppressing laminin-411 and checkpoint PD-1 showed enhanced anti-tumor effect with upregulation of genes coding for apoptotic Caspase 3 and IFNγ, and reduction of proliferation markers EGFR, c-Myc and Ki-67. Conclusion: Study describes novel GBM treatment strategy via NBCs crossing blood-brain barrier and targeting critical ECM and immune components of tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma. Citation Format: Alexander V. Ljubimov, Rameshwar Patil, Hui Ding, Liron Israel, Eggehard Holler, Julia Y. Ljubimova, Tao Sun, Keith L. Black. Brain delivery of clinically suitable nanobioconjugates to inhibit glioblastoma growth through extracellular matrix-immune cell crosstalk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 575.
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Chou, Szu-Ting, Rameshwar Patil, Anna Galstyan, Pallavi R. Gangalum, Webster K. Cavenee, Frank B. Furnari, Vladimir A. Ljubimov, et al. "Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme." Journal of Controlled Release 244 (December 2016): 14–23. http://dx.doi.org/10.1016/j.jconrel.2016.11.001.

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Ghosh, Shubhrima, Razi Ahmad, Vikas Kumar Gautam, and Sunil Kumar Khare. "Cholesterol-oxidase-magnetic nanobioconjugates for the production of 4-cholesten-3-one and 4-cholesten-3, 7-dione." Bioresource Technology 254 (April 2018): 91–96. http://dx.doi.org/10.1016/j.biortech.2018.01.030.

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Piludu, Marco, Luca Medda, Maura Monduzzi, and Andrea Salis. "Gold Nanoparticles: A Powerful Tool to Visualize Proteins on Ordered Mesoporous Silica and for the Realization of Theranostic Nanobioconjugates." International Journal of Molecular Sciences 19, no. 7 (July 8, 2018): 1991. http://dx.doi.org/10.3390/ijms19071991.

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Rangel-Muñoz, Nathaly, Alejandra Suarez-Arnedo, Raúl Anguita, Guillem Prats-Ejarque, Johann F. Osma, Carolina Muñoz-Camargo, Ester Boix, Juan C. Cruz, and Vivian A. Salazar. "Magnetite Nanoparticles Functionalized with RNases against Intracellular Infection of Pseudomonas aeruginosa." Pharmaceutics 12, no. 7 (July 6, 2020): 631. http://dx.doi.org/10.3390/pharmaceutics12070631.

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Current treatments against bacterial infections have severe limitations, mainly due to the emergence of resistance to conventional antibiotics. In the specific case of Pseudomonas aeruginosa strains, they have shown a number of resistance mechanisms to counter most antibiotics. Human secretory RNases from the RNase A superfamily are proteins involved in a wide variety of biological functions, including antimicrobial activity. The objective of this work was to explore the intracellular antimicrobial action of an RNase 3/1 hybrid protein that combines RNase 1 high catalytic and RNase 3 bactericidal activities. To achieve this, we immobilized the RNase 3/1 hybrid on Polyetheramine (PEA)-modified magnetite nanoparticles (MNPs). The obtained nanobioconjugates were tested in macrophage-derived THP-1 cells infected with Pseudomonas aeruginosa PAO1. The obtained results show high antimicrobial activity of the functionalized hybrid protein (MNP-RNase 3/1) against the intracellular growth of P. aeruginosa of the functionalized hybrid protein. Moreover, the immobilization of RNase 3/1 enhances its antimicrobial and cell-penetrating activities without generating any significant cell damage. Considering the observed antibacterial activity, the immobilization of the RNase A superfamily and derived proteins represents an innovative approach for the development of new strategies using nanoparticles to deliver antimicrobials that counteract P. aeruginosa intracellular infection.
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Raghavendra, Tripti, Arpana Basak, Lalit M. Manocha, Amita R. Shah, and Datta Madamwar. "Robust nanobioconjugates of Candida antarctica lipase B – Multiwalled carbon nanotubes: Characterization and application for multiple usages in non-aqueous biocatalysis." Bioresource Technology 140 (July 2013): 103–10. http://dx.doi.org/10.1016/j.biortech.2013.04.071.

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Ljubimova, Julia, Hui Ding, Anna Galstyan, Antonella Chiechi, San Tao, Eketerina Shatalova, Manuel Penichet, Alexander Ljubimov, Eggehard Holler, and Keith Black. "SCDT-39. NANOBIOCONJUGATES CROSSING BBB FOR DELIVERY OF CHECKPOINT INHIBITORS AND ACTIVATION OF LOCAL BRAIN TUMOR IMMUNE SYSTEMS FOR GLIOMA TREATMENT." Neuro-Oncology 19, suppl_6 (November 2017): vi272—vi273. http://dx.doi.org/10.1093/neuonc/nox168.1120.

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Say, Rıdvan, Gözde Aydoğan Kılıç, Ayça Atılır Özcan, Deniz Hür, Filiz Yılmaz, Adil Denizli, and Arzu Ersöz. "Bioconjugated and Cross-Linked Bionanostructures for Bifunctional Immunohistochemical Labeling." Microscopy and Microanalysis 18, no. 2 (March 13, 2012): 324–30. http://dx.doi.org/10.1017/s1431927611012840.

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AbstractThe present study describes the development and use of a new bioconjugate combining targeted quantum dot labeling with an immunoperoxidase method and explores whether these bioconjugates could specifically and effectively label Cu/Zn superoxide dismutase (SOD1). The new bioconjugate is designed for the examination of samples both under fluorescent and bright-field microscopy at the same time. For this purpose chlorobis(2-2′-bipyridyl) methacryloyl tyrosine-ruthenium(II) and bis (2-2′-bipyridyl) methacryloyltyrosine-methacryloyltryptophan-ruthenium (II) photosensitive monomers and photosensitive poly(Bis (2-2′-bipyridyl)) methacryloyltyrosine-methacryloyltryptophan-ruthenium(II) were synthesized and characterized. The anti-SOD1 antibody and horseradish peroxidase (HRD) conjugated quantum dots were prepared by using this polymer. The anti-SOD1 antibody and HRD conjugated quantum dots were used in labeling and imaging of SOD1 in rat liver sections. Quantum dot particles were observed as a bright fluorescence in their specific binding locations inside the hepatocytes. The HRD-diaminobenzidine reaction product was observed as brown-colored particles at the same locations under bright-field microscopy. Structural details of the tissue sections could be examined at the same time. The conjugation protocol is simple; the bioconjugate is applicable for efficient cell labeling and can be adapted for imaging of other targets in different tissues. Also, the prepared nanobioconjugates have mechanic stability and can be used for a long period.
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González, Cristina, Luis H. Reyes, Carolina Muñoz-Camargo, and Juan C. Cruz. "Synthesis, Characterization, and Functionalization of Chitosan and Gelatin Type B Nanoparticles to Develop Novel Highly Biocompatible Cell-Penetrating Agents." Materials Proceedings 4, no. 1 (November 10, 2020): 30. http://dx.doi.org/10.3390/iocn2020-07816.

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Nowadays, nanoparticles (NPs) are used to make safe and more effective biomedical technologies for applications in highly targeted therapeutics and drug-delivery vehicles. This helps avoid low cellular penetration and accumulation of the drug in intracellular endosomal compartments that are not of interest to a particular therapy. A way to enhance therapeutic efficiency is through nanoparticle loading systems. This study aims to develop low molecular weight (LMW) and high molecular weight (HMW) chitosan and type B gelatin NPs. To enhance cell penetration, the NPs were interfaced with the translocating peptide Buforin II. The obtained nanobioconjugates were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), confocal microscopy, and transmission electron microscopy (TEM). Their size and surface zeta potential were estimated via DLS (Zetasizer Nano). Furthermore, to visualize their endosomal escape, the NPs were marked with the fluorophore Rhodamine B and imaged with the aid of confocal microscopy. The FTIR results showed bands corresponding to the polymers and Buforin II after conjugation. The average NPs diameters were about 250 nm. The zeta potential of the chitosan NPs approached neutrality, which may be problematic due to low colloidal stability. The gelatin zeta potential of −7 mV was closer to the value required for colloidal stability, i.e., ±10 mV. SEM microscopy of LMW and HMW chitosan NPs showed a round-shape and oval morphology, respectively, while the gelatin NPs had a filamentous morphology. SEM also shows agglomerates of the NPs. TEM microscopy results confirmed the LMW chitosan NPs morphology and showed that their nominal size was 5–10 nm.
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Hegedüs, Imre, Kitti Andreidesz, József L. Szentpéteri, Zoltán Kaleta, László Szabó, Krisztián Szigeti, Balázs Gulyás, Parasuraman Padmanabhan, Ferenc Budan, and Domokos Máthé. "The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc." International Journal of Molecular Sciences 23, no. 19 (September 22, 2022): 11165. http://dx.doi.org/10.3390/ijms231911165.

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Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.
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Saha, Arindam, SK Basiruddin, Amit Ranjan Maity, and Nikhil R. Jana. "Synthesis of Nanobioconjugates with a Controlled Average Number of Biomolecules between 1 and 100 per Nanoparticle and Observation of Multivalency Dependent Interaction with Proteins and Cells." Langmuir 29, no. 45 (October 28, 2013): 13917–24. http://dx.doi.org/10.1021/la402699a.

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Flemming, Alexandra. "Nanobioconjugate shrinks brain tumours." Nature Reviews Drug Discovery 9, no. 12 (November 19, 2010): 917. http://dx.doi.org/10.1038/nrd3332.

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Yuan, Hengfeng, Wen Jiang, Christina A. von Roemeling, Yaqing Qie, Xiujie Liu, Yuanxin Chen, Yifan Wang, et al. "Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy." Nature Nanotechnology 12, no. 8 (May 1, 2017): 763–69. http://dx.doi.org/10.1038/nnano.2017.69.

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Cristóvão, Raquel O., Mafalda R. Almeida, Maria A. Barros, João C. F. Nunes, Rui A. R. Boaventura, José M. Loureiro, Joaquim L. Faria, et al. "Development and characterization of a novel l-asparaginase/MWCNT nanobioconjugate." RSC Advances 10, no. 52 (2020): 31205–13. http://dx.doi.org/10.1039/d0ra05534d.

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Moisă, Mădălina Elena, László Csaba Bencze, Csaba Paizs, and Monica-Ioana Toșa. "Continuous-flow enzymatic kinetic resolution mediated by a lipase nanobioconjugate." Studia Universitatis Babeș-Bolyai Chemia 64, no. 2 T1 (June 30, 2019): 79–86. http://dx.doi.org/10.24193/subbchem.2019.2.07.

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48

Bartha-Vári, Judith-Hajnal, Mădălina Elena Moisă, László Csaba Bencze, Florin-Dan Irimie, Csaba Paizs, and Monica Ioana Toșa. "Efficient Biodiesel Production Catalyzed by Nanobioconjugate of Lipase from Pseudomonas fluorescens." Molecules 25, no. 3 (February 3, 2020): 651. http://dx.doi.org/10.3390/molecules25030651.

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The Amano lipase from Pseudomonas fluorescens (L-AK) was covalently immobilized on various carbon nanomaterials (functionalized single-walled carbon nanotubes and graphene oxide) and tested for biodiesel production. Using the most active lipase preparation (covalently immobilized L-AK on SwCNTNH2 derivatized with glycerol diglycidyl ether) under optimal conditions, quasi-complete conversion (>99%) of sunflower oil was obtained after only 4 h reaction time. Moreover, the biocatalyst maintained more than 99% of its initial activity in the batch system after multiple recycling experiments.
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Chakraborty, Atanu, Chumki Dalal, and Nikhil R. Jana. "Colloidal Nanobioconjugate with Complementary Surface Chemistry for Cellular and Subcellular Targeting." Langmuir 34, no. 45 (April 26, 2018): 13461–71. http://dx.doi.org/10.1021/acs.langmuir.8b00376.

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Guldu, Ozge Kozgus, Perihan Unak, and Suna Timur. "A novel theranostic nanobioconjugate: 125/131I labeled phenylalanine conjugated boron nitride nanotubes." Journal of Radioanalytical and Nuclear Chemistry 311, no. 3 (December 3, 2016): 1751–62. http://dx.doi.org/10.1007/s10967-016-5127-4.

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