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Автор: Grafiati

Опубліковано: 7 липня 2024

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1

TAN, AMELIA LI MIN, ALISA XUE LING LIM, YITING ZHU, YI YAN YANG, and MAJAD KHAN. "CATIONIC BOLAAMPHIPHILES FOR GENE DELIVERY." COSMOS 10, no. 01 (December 2014): 25–38. http://dx.doi.org/10.1142/s0219607714400059.

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Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

2

Bengali, Zain, and Lonnie D. Shea. "Gene Delivery by Immobilization to Cell-Adhesive Substrates." MRS Bulletin 30, no. 9 (September 2005): 659–62. http://dx.doi.org/10.1557/mrs2005.193.

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AbstractBiomaterials can potentially enhance the delivery of viral and nonviral vectors for both basic science and clinical applications.Vectors typically consist of nucleic acids (DNA, RNA) packaged with proteins, lipids, or cationic polymers, which facilitate cellular internalization and trafficking. These vectors can associate with biomaterials that support cell adhesion, a process we term substrate-mediated delivery. Substrate immobilization localizes the DNA and the delivery vector to the cellular microenvironment.The interaction between the vector and substrate must be appropriately balanced to mediate immobilization, yet allow for cellular internalization. Balancing the binding between the biomaterial and the vector is dependent upon the surface chemistries of the material and the vector, which can be designed to provide both specific (e.g., biotin–avidin, the strongest known noncovalent interaction between a protein and its ligand) and nonspecific (e.g., van der Waals) interactions. In this review, we describe the biomaterial and vector properties that mediate binding and gene transfer, identify potential applications, and present opportunities for further development.

3

Nakayama, Yasuhide, Takeshi Masuda, Makoto Nagaishi, Michiko Hayashi, Moto Ohira, and Mariko Harada-Shiba. "High Performance Gene Delivery Polymeric Vector: Nano-Structured Cationic Star Polymers (Star Vectors)." Current Drug Delivery 2, no. 1 (January 1, 2005): 53–57. http://dx.doi.org/10.2174/1567201052772825.

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4

Porter, Colin D., Katalin V. Lukacs, Gary Box, Yasuhiro Takeuchi, and Mary K. L. Collins. "Cationic Liposomes Enhance the Rate of Transduction by a Recombinant Retroviral Vector In Vitro and In Vivo." Journal of Virology 72, no. 6 (June 1, 1998): 4832–40. http://dx.doi.org/10.1128/jvi.72.6.4832-4840.1998.

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ABSTRACT Cationic liposomes enhanced the rate of transduction of target cells with retroviral vectors. The greatest effect was seen with the formulation DC-Chol/DOPE, which gave a 20-fold increase in initial transduction rate. This allowed an efficiency of transduction after brief exposure of target cells to virus plus liposome that could be achieved only after extensive exposure to virus alone. Enhancement with DC-Chol/DOPE was optimal when stable virion-liposome complexes were preformed. The transduction rate for complexed virus, as for virus used alone or with the polycation Polybrene, showed first-order dependence on virus concentration. Cationic liposomes, but not Polybrene, were able to mediate envelope-independent transduction, but optimal efficiency required envelope-receptor interaction. When virus complexed with DC-Chol/DOPE was used to transduce human mesothelioma xenografts, transduction was enhanced four- to fivefold compared to that for virus alone. Since the efficacy of gene therapy is dependent on the number of cells modified, which is in turn dependent upon the balance between transduction and biological clearance of the vector, the ability of cationic liposomes to form stable complexes with retroviral vectors and enhance their rate of infection is likely to be important for in vivo application.

5

Guo, Man, Yingcai Meng, Xiaoqun Qin та Wenhu Zhou. "Dopamine-Grafted Hyaluronic Acid Coated Hyperbranched Poly(β-Amino Esters)/DNA Nano-Complexes for Enhanced Gene Delivery and Biosafety". Crystals 11, № 4 (29 березня 2021): 347. http://dx.doi.org/10.3390/cryst11040347.

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Gene therapy has attracted particular attention for the treatment of various genetic diseases, and the development of gene delivery vectors is of utmost importance for in vivo applications of gene drugs. Various cationic polymers with high nucleic acid loading and intracellular transfection efficiency have been reported, however, their biological applications are limited by potential toxicity. Surface modification is a robust solution to detoxify the cationic vectors, but this can inevitably weaken the transfection efficiency. To address this dilemma, we reported the ability of a dopamine (DA)-grafted hyaluronic acid (HA) to modify gene vectors for enhanced gene delivery and biosafety. The nano-vector was formed by using branched poly(β-amino esters) (PAEs), and surface coating with HA-DA to form a core-shell nano-structure via electrostatic attraction. Upon HA-DA modification, the biosafety of the gene delivery vehicle was improved, as demonstrated by the cell cytotoxicity assay and hemolysis test. Notably, the nano-system displayed a DA-dependent transfection efficiency, in which a higher DA grafting degree resulted in better efficacy. This can be explained by the adhesive nature of DA, facilitating cell membrane interaction, as well as DA receptor mediated active targeting. At the optimal DA grafting ratio, the nano-system achieved a transfection efficiency even better than that of commonly used polyethylenimine (PEI) vectors. Together with its excellent biocompatibility, the vector presented here holds great promise for gene delivery applications.

6

Marquet, Franck, Viorica Patrulea та Gerrit Borchard. "Comparison of triblock copolymeric micelles based on α- and ε-poly(L-lysine): a Cornelian choice". Polymer Journal 54, № 2 (13 жовтня 2021): 199–209. http://dx.doi.org/10.1038/s41428-021-00552-5.

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AbstractDue to the lack of safe carriers for the delivery of small interfering RNA (siRNA), clinical applications of nucleotide-based therapeutics have been limited. In this study, biodegradable amphiphilic triblock copolymers with tailored molecular weights for each block composed of methoxy poly(ethylene glycol) (2000 g/mol), poly(L-lysine) (1300 g/mol) and poly(D,L-lactic acid) (1800 g/mol) (mPEG45-α-PLL10-PLA25) were synthesized and fully characterized. The peptide synthesis was carried out on a solid phase to limit the presence of cationic charges. The arrangement and availability of cationic amino groups within a micellar vector were investigated to determine the colloidal stability as well as the predisposition of these systems to vectorize siRNAs in addition to their already known ability to improve the solubility of hydrophobic compounds. For this purpose, a triblock copolymer containing an epsilon poly(L-lysine) was synthesized similarly. Accordingly, the arrangement of the cationic segment modifies the rigidity involving a complexation constraint due to limited cationic charges available on the surface, which can compromise the efficiency of delivery into cells. In addition, the two vectors were biocompatible in different human cell lines.

7

Budker, Vladimir, Vladimir Gurevich, James E. Hagstrom, Fedor Bortzov, and Jon A. Wolff. "pH-sensitive, cationic liposomes: A new synthetic virus-like vector." Nature Biotechnology 14, no. 6 (June 1996): 760–64. http://dx.doi.org/10.1038/nbt0696-760.

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8

Ito, Akira, Tetsuya Takahashi, Yujiro Kameyama, Yoshinori Kawabe, and Masamichi Kamihira. "Magnetic Concentration of a Retroviral Vector Using Magnetite Cationic Liposomes." Tissue Engineering Part C: Methods 15, no. 1 (March 2009): 57–64. http://dx.doi.org/10.1089/ten.tec.2008.0275.

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9

Natsume, Atsushi, Masaaki Mizuno, Yasushi Ryuke, and Jun Yoshida. "Cationic Liposome Conjugation to Recombinant Adenoviral Vector Reduces Viral Antigenicity." Japanese Journal of Cancer Research 91, no. 4 (April 2000): 363–67. http://dx.doi.org/10.1111/j.1349-7006.2000.tb00953.x.

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10

El-Mahdy, Ahmed F. M., Takayuki Shibata, Tsutomu Kabashima, Qinchang Zhu, and Masaaki Kai. "Delivery of siRNA using siRNA/cationic vector complexes encapsulated in dendrimer-like polymeric DNAs." RSC Advances 5, no. 41 (2015): 32775–85. http://dx.doi.org/10.1039/c5ra01032b.

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11

Berchel, Mathieu, Tony Le Gall, Olivier Lozach, Jean-Pierre Haelters, Tristan Montier, and Paul-Alain Jaffrès. "Lipophosphoramidate-based bipolar amphiphiles: their syntheses and transfection properties." Organic & Biomolecular Chemistry 14, no. 10 (2016): 2846–53. http://dx.doi.org/10.1039/c5ob02512e.

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12

Cui, Pengfei, Jianhe Ma, Huihui Zhang, Lin Qiu, Shuwen Zhou, Cheng Wang, Xinye Ni, Pengju Jiang, and Jianhao Wang. "Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer." Journal of Biomedical Nanotechnology 18, no. 2 (February 1, 2022): 435–45. http://dx.doi.org/10.1166/jbn.2022.3252.

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Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K’s indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

13

Ilies, Marc, William Seitz, and Alexandru Balaban. "Cationic Lipids in Gene Delivery: Principles, Vector Design and Therapeutical Applications." Current Pharmaceutical Design 8, no. 27 (December 1, 2002): 2441–73. http://dx.doi.org/10.2174/1381612023392748.

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14

Roux, D., P. Chenevier, T. Pott, L. Navailles, O. Regev, and O. Monval. "Conception and Realization of a Non-Cationic Non-Viral DNA Vector." Current Medicinal Chemistry 11, no. 2 (January 1, 2004): 169–77. http://dx.doi.org/10.2174/0929867043456133.

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15

Yang, Bin, Yun-xia Sun, Wen-jie Yi, Juan Yang, Chen-wei Liu, Han Cheng, Jun Feng, Xian-zheng Zhang, and Ren-xi Zhuo. "A linear-dendritic cationic vector for efficient DNA grasp and delivery." Acta Biomaterialia 8, no. 6 (July 2012): 2121–32. http://dx.doi.org/10.1016/j.actbio.2012.02.013.

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16

Matsumoto, Megumi, Reiko Kishikawa, Tomoaki Kurosaki, Hiroo Nakagawa, Nobuhiro Ichikawa, Tomoyuki Hamamoto, Hideto To, Takashi Kitahara, and Hitoshi Sasaki. "Hybrid vector including polyethylenimine and cationic lipid, DOTMA, for gene delivery." International Journal of Pharmaceutics 363, no. 1-2 (November 2008): 58–65. http://dx.doi.org/10.1016/j.ijpharm.2008.07.010.

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17

Vemana, Hari Priya, Aishwarya Saraswat, Shraddha Bhutkar, Ketan Patel, and Vikas V. Dukhande. "A novel gene therapy for neurodegenerative Lafora disease via EPM2A-loaded DLinDMA lipoplexes." Nanomedicine 16, no. 13 (June 2021): 1081–95. http://dx.doi.org/10.2217/nnm-2020-0477.

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Aim: To develop novel cationic liposomes as a nonviral gene delivery vector for the treatment of rare diseases, such as Lafora disease – a neurodegenerative epilepsy. Materials & methods: DLinDMA and DOTAP liposomes were formulated and characterized for the delivery of gene encoding laforin and expression of functional protein in HEK293 and neuroblastoma cells. Results: Liposomes with cationic lipids DLinDMA and DOTAP showed good physicochemical characteristics. Nanosized DLinDMA liposomes demonstrated desired transfection efficiency, negligible hemolysis and minimal cytotoxicity. Western blotting confirmed successful expression and glucan phosphatase assay demonstrated the biological activity of laforin. Conclusion: Our study is a novel preclinical effort in formulating cationic lipoplexes containing plasmid DNA for the therapy of rare genetic diseases such as Lafora disease.

18

Matai, Ishita, and P. Gopinath. "Hydrophobic myristic acid modified PAMAM dendrimers augment the delivery of tamoxifen to breast cancer cells." RSC Advances 6, no. 30 (2016): 24808–19. http://dx.doi.org/10.1039/c6ra02391f.

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In the present study, cationic generation 5 polyamido amine (G5 PAMAM) dendrimers were hydrophobically modified by grafting the surface with lipid-like myristic acid (My) tails to augment their potential as a drug delivery vector in vitro.

19

Zhang, Fanghua, Chao Zhang, Shuangqing Fu, Huandi Liu, Mengnan Han, Xueyu Fan, Honglei Zhang, and Wei Li. "Amphiphilic Cationic Peptide-Coated PHA Nanosphere as an Efficient Vector for Multiple-Drug Delivery." Nanomaterials 12, no. 17 (August 31, 2022): 3024. http://dx.doi.org/10.3390/nano12173024.

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Amphiphilic core–shell (ACS) nanoparticles are gaining increasing research interest for multi-drug delivery in cancer therapy. In this work, a new cationic peptide-coated PHA nanosphere was prepared by self-assembly of a hydrophobic core of biodegradable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a hydrophilic shell of fusion proteins of PHA granule-associated protein (PhaP) and cationic peptide RALA through a strong hydrophobic effect. The hydrophobic drug curcumin (Cur) was encapsulated in PHBHHx nanoparticles. The chemotherapy drug 5-fluorouracil (5-FU) was administered in the form of its metabolite oligomeric 5-fluorodeoxyuridine (FUdR). Fifteen consecutive FUdR (FUdR15S) were adsorbed on the surface of PHBHHx nanoparticles by electrostatic interaction with RALA to form Cur@PHBX-PR/FUdR15S. Such amphiphilic cationic nanospheres had 88.3% EE of Cur and the drug loading of Cur and FUdR were 7.8% and 12.1%. The dual-drug-loaded nanospheres showed a time-differential release of Cur and FUdR. In addition, Cur@PHBX-PR/FUdR15S exhibited excellent anticancer activity and played a vital role in promoting the synergistic effect of FUdR and Cur in gastric cancer cells. The exploration of antitumor mechanisms demonstrated that Cur improved the activity of apoptosis-related proteins and cancer cells sensitized to FUdR. This amphiphilic core–shell system can serve as a general platform for sequential delivery of multiple drugs to treat several cancer cells.

20

Kurosaki, Tomoaki, Takashi Kitahara, Mugen Teshima, Koyo Nishida, Junzo Nakamura, Mikiro Nakashima, Hideto To, Hiromitsu Hukuchi, Tomoyuki Hamamoto, and Hitoshi Sasaki. "Exploitation of De Novo Helper-Lipids for Effective Gene Delivery." Journal of Pharmacy & Pharmaceutical Sciences 11, no. 4 (January 5, 2009): 56. http://dx.doi.org/10.18433/j31s3b.

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Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

21

Hoekstra, D., J. Rejman, L. Wasungu, F. Shi, and I. Zuhorn. "Gene delivery by cationic lipids: in and out of an endosome." Biochemical Society Transactions 35, no. 1 (January 22, 2007): 68–71. http://dx.doi.org/10.1042/bst0350068.

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Cationic lipids are exploited as vectors (‘lipoplexes’) for delivering nucleic acids, including genes, into cells for both therapeutic and cell biological purposes. However, to meet therapeutic requirements, their efficacy needs major improvement, and better defining the mechanism of entry in relation to eventual transfection efficiency could be part of such a strategy. Endocytosis is the major pathway of entry, but the relative contribution of distinct endocytic pathways, including clathrin- and caveolae-mediated endocytosis and/or macropinocytosis is as yet poorly defined. Escape of DNA/RNA from endosomal compartments is thought to represent a major obstacle. Evidence is accumulating that non-lamellar phase changes of the lipoplexes, facilitated by intracellular lipids, which allow DNA to dissociate from the vector and destabilize endosomal membranes, are instrumental in plasmid translocation into the cytosol, a prerequisite for nuclear delivery. To further clarify molecular mechanisms and to appreciate and overcome intracellular hurdles in lipoplex-mediated gene delivery, quantification of distinct steps in overall transfection and proper model systems are required.

22

Sanchez-Martos, Miguel, Gema Martinez-Navarrete, Adela Bernabeu-Zornoza, Lawrence Humphreys, and Eduardo Fernandez. "Evaluation and Optimization of Poly-d-Lysine as a Non-Natural Cationic Polypeptide for Gene Transfer in Neuroblastoma Cells." Nanomaterials 11, no. 7 (July 5, 2021): 1756. http://dx.doi.org/10.3390/nano11071756.

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Cationic polypeptides and cationic polymers have cell-penetrating capacities and have been used in gene transfer studies. In this study, we investigate the capability of a polymer of d-lysine (PDL), a chiral form of α–Poly-lysine, as a possible nonviral vector for releasing genetic materials to neuroblastoma cells and evaluate its stability against proteases. We tested and compared its transfection effectiveness in vitro as a vehicle for the EGFP plasmid DNA (pDNA) reporter in the SH-SY5Y human neuroblastoma, HeLa, and 3T3 cell lines. Using fluorescent microscopy and flow cytometry, we demonstrated high transfection efficiencies based on EGFP fluorescence in SH-SY5Y cells, compared with HeLa and 3T3. Our results reveal PDL as an efficient vector for gene delivery specifically in the SH-SY5Y cell line and suggest that PDL can be used as a synthetic cell-penetrating polypeptide for gene therapy in neuroblastoma cells.

23

Newland, B., A. Aied, A. V. Pinoncely, Y. Zheng, T. Zhao, H. Zhang, R. Niemeier, E. Dowd, A. Pandit, and W. Wang. "Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain." Nanoscale 6, no. 13 (2014): 7526–33. http://dx.doi.org/10.1039/c3nr06737h.

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A cationic knot structured transfection vector showed a more favorable transfection profile for a neural cell type compared to other polyplexes whilst maintaining cell viability at over 80% after four days of culture and could mediate luciferase overexpression in the adult brain.

24

Butt, Muhammad Hammad, Muhammad Zaman, Abrar Ahmad, Rahima Khan, Tauqeer Hussain Mallhi, Mohammad Mehedi Hasan, Yusra Habib Khan, et al. "Appraisal for the Potential of Viral and Nonviral Vectors in Gene Therapy: A Review." Genes 13, no. 8 (July 30, 2022): 1370. http://dx.doi.org/10.3390/genes13081370.

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Over the past few decades, gene therapy has gained immense importance in medical research as a promising treatment strategy for diseases such as cancer, AIDS, Alzheimer’s disease, and many genetic disorders. When a gene needs to be delivered to a target cell inside the human body, it has to pass a large number of barriers through the extracellular and intracellular environment. This is why the delivery of naked genes and nucleic acids is highly unfavorable, and gene delivery requires suitable vectors that can carry the gene cargo to the target site and protect it from biological degradation. To date, medical research has come up with two types of gene delivery vectors, which are viral and nonviral vectors. The ability of viruses to protect transgenes from biological degradation and their capability to efficiently cross cellular barriers have allowed gene therapy research to develop new approaches utilizing viruses and their different genomes as vectors for gene delivery. Although viral vectors are very efficient, science has also come up with numerous nonviral systems based on cationic lipids, cationic polymers, and inorganic particles that provide sustainable gene expression without triggering unwanted inflammatory and immune reactions, and that are considered nontoxic. In this review, we discuss in detail the latest data available on all viral and nonviral vectors used in gene delivery. The mechanisms of viral and nonviral vector-based gene delivery are presented, and the advantages and disadvantages of all types of vectors are also given.

25

Tan, Zhi Lei, Bei Xing, Shi Ru Jia та Fang Lian Yao. "Preparation of ε-Polylysine Modified Silica Nanoparticles". Advanced Materials Research 712-715 (червень 2013): 511–14. http://dx.doi.org/10.4028/www.scientific.net/amr.712-715.511.

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Gene vector system is the key to realize gene transduction and therapy. A proper gene vector can introduce the target gene into cells securely, efficiently, controllably and easily, and achieve purposes of gene transfection and disease treatment after its expression. ε-polylysine (ε-PL),which is rich in cationic and has high penetrability through biological membrane,can be applied in DNA carrier. In this study, we presented a novel approach for preparing ε-polylysine modified silica nanoparticles and combinating them with plasmid DNA.

26

Vighi, Eleonora, and Eliana Leo. "Studying thein vitrobehavior of cationic solid lipid nanoparticles as a nonviral vector." Nanomedicine 7, no. 1 (January 2012): 9–12. http://dx.doi.org/10.2217/nnm.11.168.

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27

Vitor, Micaela T., Patricia C. Bergami Santos, Jose A. M. Barbuto, and Lucimara G. de la Torre. "Cationic Liposomes as Non-viral Vector for RNA Delivery in Cancer Immunotherapy." Recent Patents on Drug Delivery & Formulation 7, no. 2 (May 1, 2013): 99–110. http://dx.doi.org/10.2174/18722113113079990010.

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28

He, Zhijian, Lei Miao, Rainer Jordan, Devika S-Manickam, Robert Luxenhofer, and Alexander V. Kabanov. "A Low Protein Binding Cationic Poly(2-oxazoline) as Non-Viral Vector." Macromolecular Bioscience 15, no. 7 (April 2, 2015): 1004–20. http://dx.doi.org/10.1002/mabi.201500021.

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29

Ochoa-Sánchez, C. I., K. Ochoa Lara, J. M. Martínez-Soto, A. Martínez-Higuera, R. A. Iñiguez-Palomares, R. Moreno-Corral, E. Rodríguez-León, A. Soto-Guzmán, and C. Rodríguez-Beas. "Physicochemical Characterization and Viability Assays of a Promising Formulation of Liposomes (DODAB-DOPC) in Complexation with ctDNA." Journal of Nanomaterials 2022 (June 25, 2022): 1–10. http://dx.doi.org/10.1155/2022/3085103.

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The search of new genetic vectors that improve the efficacy of gene delivery into diseased cells has led to the creation of several vector formulations that promote effectiveness in applications. However, DNA affinity to vectors as well as vector/DNA complex stability remains a problem to be solved. Here, we study lipoplexes made of DODAB-DOPC cationic liposomes (CL) and calf thymus DNA (ctDNA) as a preliminary cargo gene model of a novel vector formulation to improve DNA delivery efficacy and affinity. Physicochemical characterization was carried out by Z -potential ( ζ ), light scattering, ultraviolet, fluorescence spectra, confocal, and electronic microscopy to prove CL and ctDNA complexation and high affinity. Through this approach, ζ and light scattering results indicate an effective CL and ctDNA complexation; CL charge decreases as ctDNA concentration increases. Obtained spectra from UV and fluorescence show high affinity between CL and ctDNA. This can be also verified by confocal microscopy images and electronic microscopy micrographs. All experiments show effective binding between CL and ctDNA, and fluorescence experiments show EtBr displacing as CL concentration increments. CL cytotoxicity assays show high viability when ctDNA is complexed; these results are comparable with those obtained using Lipofectamine 2000. Easy complexation and low cytotoxicity make them a promising formulation for gene delivery. The obtained results from this work motivate us to keep searching for new genetic vector formulations, which could reduce its cytotoxic effect and improve its transfection efficiency, in addition to the low cost of production compared with some commercial products.

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Chen, Si, Jiguang Li, Xiaoyu Ma, Fan Liu, and Guoping Yan. "Cationic Peptide-Modified Gold Nanostars as Efficient Delivery Platform for RNA Interference Antitumor Therapy." Polymers 13, no. 21 (October 30, 2021): 3764. http://dx.doi.org/10.3390/polym13213764.

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siRNA interference therapy can silence tumor cell target genes and specifically regulate tumor cell behavior and function, which is an effective antitumor therapy. However, in somatic circulation, naked siRNAs are not only susceptible to degrade, but it is also difficult to realize the tumor cells’ internalization. Therefore, novel siRNA delivery vectors that could promote efficacy need to be developed urgently. Here, we designed high-surface gold nanostars (GNS-P) which are decorated with cationic tumor-targeting peptide as an efficient and functional siRNA delivery nanoplatform for tumor therapy. The positively charged amino acid sequence and huge surface area enabled the vector to load a large amount of siRNA, while the tumor-targeting peptide sequence and nano size enabled it to rapidly and precisely target the tumor regions for fast and effective siRNA delivery. This tumor-targeting nanoplatform, GNS-P, displayed good biocompatibility, low toxicity and an extraordinary tumor accumulation capability.

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Bragonzi, A., G. Dina, A. Villa, G. Calori, A. Biffi, C. Bordignon, B. M. Assael, and M. Conese. "Biodistribution and transgene expression with nonviral cationic vector/DNA complexes in the lungs." Gene Therapy 7, no. 20 (October 2000): 1753–60. http://dx.doi.org/10.1038/sj.gt.3301282.

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Hattori, Yoshiyuki, and Yoshie Maitani. "Low-Molecular-Weight Polyethylenimine Enhanced Gene Transfer by Cationic Cholesterol-Based Nanoparticle Vector." Biological & Pharmaceutical Bulletin 30, no. 9 (2007): 1773–78. http://dx.doi.org/10.1248/bpb.30.1773.

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Ouyang, Defang, Hong Zhang, Dirk-Peter Herten, Harendra S. Parekh, and Sean C. Smith. "Structure, Dynamics, and Energetics of siRNA−Cationic Vector Complexation: A Molecular Dynamics Study." Journal of Physical Chemistry B 114, no. 28 (July 22, 2010): 9220–30. http://dx.doi.org/10.1021/jp911906e.

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34

Fominaya, Jes�s, Mar�a Gasset, Rosana Garc�a, Fernando Roncal, Juan Pablo Albar, and Antonio Bernad. "An optimized amphiphilic cationic peptide as an efficient non-viral gene delivery vector." Journal of Gene Medicine 2, no. 6 (2000): 455–64. http://dx.doi.org/10.1002/1521-2254(200011/12)2:6<455::aid-jgm145>3.0.co;2-o.

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35

Munisso, Maria Chiara, Atsushi Mahara, Yoichi Tachibana, Jeong Hun Kang, Satoshi Obika, and Tetsuji Yamaoka. "Hepatocyte-Specific Gene Delivery with Galactose-Bearing Cationic Polymers with Different Molecular Structures." Advances in Science and Technology 86 (September 2012): 86–91. http://dx.doi.org/10.4028/www.scientific.net/ast.86.86.

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Since the promising virus -based gene therapies are often limited by problems such as the immunity of virus itself, the development of an efficient non-viral vector is of prime importance. For this reason, several synthetic nonviral polymeric carriers including cationic sequences have been molecularly designed. It is well known that the polymeric carriers with some cationic groups buffer the endosomal pH resulting in the enhanced transfection efficiency, but also in a relatively high toxicity. In the last decades, the polymers bearing pendant carbohydrates (glycopolymers) was proved to have relatively less toxic. Since the glycopolymers may not only decrease the toxicity of the cationic chain but also serve as targeting agent, we have rationally designed new glycopolymer-based gene delivery carriers. The interaction of carrier/gene polyplexes with hepatocytes and their intracellular trafficking were investigated in vitro. Our results show the significant efficacy of the galactose moieties on the uptake by hepatocytes, in a ligand specific manner.

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Cao, Ye, Yang Fei Tan, Yee Shan Wong, Melvin Wen Jie Liew, and Subbu Venkatraman. "Recent Advances in Chitosan-Based Carriers for Gene Delivery." Marine Drugs 17, no. 6 (June 25, 2019): 381. http://dx.doi.org/10.3390/md17060381.

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Approximately 4000 diseases are associated with malfunctioning genes in a particular cell type. Gene-based therapy provides a platform to modify the disease-causing genes expression at the cellular level to treat pathological conditions. However, gene delivery is challenging as these therapeutic genes need to overcome several physiological and intracellular barriers in order, to reach the target cells. Over the years, efforts have been dedicated to develop efficient gene delivery vectors to overcome these systemic barriers. Chitosan, a versatile polysaccharide, is an attractive non-viral vector material for gene delivery mainly due to its cationic nature, biodegradability and biocompatibility. The present review discusses the design factors that are critical for efficient gene delivery/transfection and highlights the recent progress of gene therapy using chitosan-based carriers.

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Jafari, Amin, Nika Rajabian, Guojian Zhang, Mohamed Alaa Mohamed, Pedro Lei, Stelios T. Andreadis, Blaine A. Pfeifer та Chong Cheng. "PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA". Materials 13, № 4 (18 лютого 2020): 898. http://dx.doi.org/10.3390/ma13040898.

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As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

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Ullah, Ihsan, Jing Zhao, Shah Rukh, Khan Muhammad, Jintang Guo, Xiang-kui Ren, Shihai Xia, Wencheng Zhang, and Yakai Feng. "A PEG-b-poly(disulfide-l-lysine) based redox-responsive cationic polymer for efficient gene transfection." Journal of Materials Chemistry B 7, no. 11 (2019): 1893–905. http://dx.doi.org/10.1039/c8tb03226b.

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39

Alamoudi, Abdullah A., Paula A. Méndez, David Workman, Andreas G. Schätzlein, and Ijeoma F. Uchegbu. "Brain Gene Silencing with Cationic Amino-Capped Poly(ethylene glycol) Polyplexes." Biomedicines 10, no. 9 (September 3, 2022): 2182. http://dx.doi.org/10.3390/biomedicines10092182.

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Therapeutic gene silencing in the brain is usually achieved using highly invasive intracranial administration methods and/or comparatively toxic vectors. In this work, we use a relatively biocompatible vector: poly(ethylene glycol) star-shaped polymer capped with amine groups (4APPA) via the nose to brain route. 4APPA complexes anti- itchy E3 ubiquitin protein ligase (anti-ITCH) siRNA to form positively charged (zeta potential +15 ± 5 mV) 150 nm nanoparticles. The siRNA-4APPA polyplexes demonstrated low cellular toxicity (IC50 = 13.92 ± 6 mg mL−1) in the A431 cell line and were three orders of magnitude less toxic than Lipofectamine 2000 (IC50 = 0.033 ± 0.04 mg mL−1) in this cell line. Cell association and uptake of fluorescently labelled siRNA bound to siRNA-4APPA nanoparticles was demonstrated using fluorescent activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM), respectively. Gene silencing of the ITCH gene was observed in vitro in the A431 cell line (65% down regulation when compared to the use of anti-ITCH siRNA alone). On intranasal dosing with fluorescently labelled siRNA-4APPA polyplexes, fluorescence was seen in the cells of the olfactory bulb, cerebral cortex and mid-brain regions. Finally, down regulation of ITCH was seen in the brain cells (54 ± 13% ITCH remaining compared to untreated controls) in a healthy rat model, following intranasal dosing of siRNA-4APPA nanoparticles (0.15 mg kg−1 siRNA twice daily for 3 days). Gene silencing in the brain may be achieved by intranasal administration of siRNA- poly(ethylene glycol) based polyplexes.

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Miller, Andrew. "The Problem with Cationic Liposome / Micelle-Based Non-Viral Vector Systems for Gene Therapy." Current Medicinal Chemistry 10, no. 14 (July 1, 2003): 1195–211. http://dx.doi.org/10.2174/0929867033457485.

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41

Fein, David E., Maria P. Limberis, Sean F. Maloney, Jack M. Heath, James M. Wilson, and Scott L. Diamond. "Cationic Lipid Formulations Alter the In Vivo Tropism of AAV2/9 Vector in Lung." Molecular Therapy 17, no. 12 (December 2009): 2078–87. http://dx.doi.org/10.1038/mt.2009.173.

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42

Guo, Xin Dong, Fanny Tandiono, Nikken Wiradharma, Dingyue Khor, Chuan Guan Tan, Majad Khan, Yu Qian, and Yi-Yan Yang. "Cationic micelles self-assembled from cholesterol-conjugated oligopeptides as an efficient gene delivery vector." Biomaterials 29, no. 36 (December 2008): 4838–46. http://dx.doi.org/10.1016/j.biomaterials.2008.07.053.

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43

Guerra-Rebollo, Marta, María Stampa, Miguel Ángel Lázaro, Anna Cascante, Cristina Fornaguera, and Salvador Borrós. "Electrostatic Coating of Viral Particles for Gene Delivery Applications in Muscular Dystrophies: Influence of Size on Stability and Antibody Protection." Journal of Neuromuscular Diseases 8, no. 5 (September 14, 2021): 815–25. http://dx.doi.org/10.3233/jnd-210662.

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Background: Duchenne Muscular Dystrophy (DMD) is one of the most common muscular dystrophies, caused by mutated forms of the dystrophin gene. Currently, the only treatment available is symptoms management. Novel approximations are trying to treat these patients with gene therapy, namely, using viral vectors. However, these vectors can be recognized by the immune system decreasing their therapeutic activity and making impossible a multidose treatment due to the induction of the humoral immunity following the first dose. Objective: Our objective is to demonstrate the feasibility of using a hybrid vector to avoid immune clearance, based on the electrostatic coating of adeno-associated virus (AAVs) vectors with our proprietary polymers. Methods: We coated model adeno-associated virus vectors by electrostatic interaction of our cationic poly (beta aminoester) polymers with the viral anionic capsid and characterized biophysical properties. Once the nanoformulations were designed, we studied their in vivo biodistribution by bioluminescence analysis and we finally studied the capacity of the polymers as potential coatings to avoid antibody neutralization. Results: We tested two polymer combinations and we demonstrated the need for poly(ethylene glycol) addition to avoid vector aggregation after coating. In vivo biodistribution studies demonstrated that viral particles are located in the liver (short times) and also in muscles (long times), the target organ. However, we did not achieve complete antibody neutralization shielding using this electrostatic coating. Conclusions: The null hypothesis stands: although it is feasible to coat viral particles by electrostatic interaction with a proprietary polymer, this strategy is not appropriate for AAVs due to their small size, so other alternatives are required as a novel treatment for DMD patients.

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De Simone, Simeone, Francesco Di Capua, Ludovico Pontoni, Andrea Giordano, and Giovanni Esposito. "Impact of Cationic Polyelectrolyte Addition on Mesophilic Anaerobic Digestion and Hydrocarbon Content of Sewage Sludge." Fermentation 8, no. 10 (October 16, 2022): 548. http://dx.doi.org/10.3390/fermentation8100548.

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The agricultural spreading of treated sewage sludge is a valid strategy in terms of circular economy for the management of this nutrient-rich waste. Anaerobic digestion (AD) can be applied to stabilize and hygienize sewage sludge, making it suitable for agricultural reuse, while producing biogas to be utilized as an energy vector. However, the presence of contaminants, including petroleum hydrocarbons, could limit the widespread agricultural utilization of sewage sludge. In this context, the impact of dewatering agents, such as cationic polyelectrolytes, on AD efficiency and hydrocarbon biodegradation has been poorly investigated, although it represents a noteworthy aspect when conditioned sludge is digested for agricultural use in centralized biogas plants. This work aims to elucidate the effect of cationic polyelectrolyte addition on biomethanation as well as the degradation and extractability of C10-C40 hydrocarbons during mesophilic AD of sewage sludge. The addition of 26.7 g/kgTS of cationic polyelectrolyte was observed to extend the AD lag phase, although similar methane yields (573–607 mLCH4 per g of degraded volatile solids) were observed for both conditioned and raw sludge. Furthermore, a significant impact on hydrocarbon degradation was observed due to chemical conditioning. Indeed, this work reveals that cationic polyelectrolytes can affect hydrocarbon extractability and suggests moreover that the presence of natural interferents (e.g., biogenic waxes) in sewage sludge may lead to an overestimation of potentially toxic C10-C40 hydrocarbon concentrations, potentially limiting the application of sludge-derived digestates in agriculture.

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Nakashima, Y., M. Yano, Y. Kobayashi, S. Moriyama, H. Sasaki, T. Toyama, H. Yamashita, et al. "Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery." Gene Therapy 10, no. 2 (January 2003): 123–30. http://dx.doi.org/10.1038/sj.gt.3301856.

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46

Yue, Xinye, Wendi Zhang, Jinfeng Xing, Biao Zhang, Liandong Deng, Shutao Guo, Jun Yang, Qiang Zhang, and Anjie Dong. "Self-assembled cationic triblock copolymer mPEG-b-PDLLA-b-PDMA nanoparticles as nonviral gene vector." Soft Matter 8, no. 7 (2012): 2252. http://dx.doi.org/10.1039/c2sm07068e.

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47

Kim, Chong-Kook, Eun-Jeong Choi, Sung-Hee Choi, Jeong-Sook Park, Khawaja Hasnain Haider, and Woong Shick Ahn. "Enhanced p53 gene transfer to human ovarian cancer cells using the cationic nonviral vector, DDC." Gynecologic Oncology 90, no. 2 (August 2003): 265–72. http://dx.doi.org/10.1016/s0090-8258(03)00248-8.

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48

Vighi, Eleonora, Monica Montanari, Miriam Hanuskova, Valentina Iannuccelli, Gilberto Coppi, and Eliana Leo. "Design flexibility influencing the in vitro behavior of cationic SLN as a nonviral gene vector." International Journal of Pharmaceutics 440, no. 2 (January 2013): 161–69. http://dx.doi.org/10.1016/j.ijpharm.2012.08.055.

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49

Ono, Ichiro, Toshiharu Yamashita, Hai-Ying Jin, Yoshinori Ito, Hirobumi Hamada, Yoshikiyo Akasaka, Masanori Nakasu, Tetsunori Ogawa, and Kowichi Jimbow. "Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy." Biomaterials 25, no. 19 (August 2004): 4709–18. http://dx.doi.org/10.1016/j.biomaterials.2003.11.038.

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Dufès, Christine, W. Nicol Keith, Alan Bilsland, Irina Proutski, Ijeoma F. Uchegbu, and Andreas G. Schätzlein. "Synthetic Anticancer Gene Medicine Exploits Intrinsic Antitumor Activity of Cationic Vector to Cure Established Tumors." Cancer Research 65, no. 18 (September 15, 2005): 8079–84. http://dx.doi.org/10.1158/0008-5472.can-04-4402.

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