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Статті в журналах з теми "Functional delivery"

Автор: Grafiati

Опубліковано: 29 березня 2025

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1

Kim, Raeyeong, and Jong Hyun Kim. "Engineered Extracellular Vesicles with Compound-Induced Cargo Delivery to Solid Tumors." International Journal of Molecular Sciences 24, no. 11 (May 27, 2023): 9368. http://dx.doi.org/10.3390/ijms24119368.

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Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers.

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2

Gibbons, Jeremy. "Free delivery (functional pearl)." ACM SIGPLAN Notices 51, no. 12 (July 19, 2018): 45–50. http://dx.doi.org/10.1145/3241625.2976005.

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3

Nakazato, Yugo, and Joji M. Otaki. "Protein Delivery to Insect Epithelial Cells In Vivo: Potential Application to Functional Molecular Analysis of Proteins in Butterfly Wing Development." BioTech 12, no. 2 (April 16, 2023): 28. http://dx.doi.org/10.3390/biotech12020028.

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Protein delivery to cells in vivo has great potential for the functional analysis of proteins in nonmodel organisms. In this study, using the butterfly wing system, we investigated a method of protein delivery to insect epithelial cells that allows for easy access, treatment, and observation in real time in vivo. Topical and systemic applications (called the sandwich and injection methods, respectively) were tested. In both methods, green/orange fluorescent proteins (GFP/OFP) were naturally incorporated into intracellular vesicles and occasionally into the cytosol from the apical surface without any delivery reagent. However, the antibodies were not delivered by the sandwich method at all, and were delivered only into vesicles by the injection method. A membrane-lytic peptide, L17E, appeared to slightly improve the delivery of GFP/OFP and antibodies. A novel peptide reagent, ProteoCarry, successfully promoted the delivery of both GFP/OFP and antibodies into the cytosol via both the sandwich and injection methods. These protein delivery results will provide opportunities for the functional molecular analysis of proteins in butterfly wing development, and may offer a new way to deliver proteins into target cells in vivo in nonmodel organisms.

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4

Kanada, Masamitsu, Michael H. Bachmann, Jonathan W. Hardy, Daniel Omar Frimannson, Laura Bronsart, Andrew Wang, Matthew D. Sylvester, et al. "Differential fates of biomolecules delivered to target cells via extracellular vesicles." Proceedings of the National Academy of Sciences 112, no. 12 (February 23, 2015): E1433—E1442. http://dx.doi.org/10.1073/pnas.1418401112.

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Extracellular vesicles (EVs), specifically exosomes and microvesicles (MVs), are presumed to play key roles in cell–cell communication via transfer of biomolecules between cells. The biogenesis of these two types of EVs differs as they originate from either the endosomal (exosomes) or plasma (MVs) membranes. To elucidate the primary means through which EVs mediate intercellular communication, we characterized their ability to encapsulate and deliver different types of macromolecules from transiently transfected cells. Both EV types encapsulated reporter proteins and mRNA but only MVs transferred the reporter function to recipient cells. De novo reporter protein expression in recipient cells resulted only from plasmid DNA (pDNA) after delivery via MVs. Reporter mRNA was delivered to recipient cells by both EV types, but was rapidly degraded without being translated. MVs also mediated delivery of functional pDNA encoding Cre recombinase in vivo to tissues in transgenic Cre-lox reporter mice. Within the parameters of this study, MVs delivered functional pDNA, but not RNA, whereas exosomes from the same source did not deliver functional nucleic acids. These results have significant implications for understanding the role of EVs in cellular communication and for development of EVs as delivery tools. Moreover, studies using EVs from transiently transfected cells may be confounded by a predominance of pDNA transfer.

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5

Barthélémy, Philippe, and Michel Camplo. "Functional Amphiphiles for Gene Delivery." MRS Bulletin 30, no. 9 (September 2005): 647–53. http://dx.doi.org/10.1557/mrs2005.191.

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AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

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6

Tai, Wanyi, and Xiaohu Gao. "Functional peptides for siRNA delivery." Advanced Drug Delivery Reviews 110-111 (February 2017): 157–68. http://dx.doi.org/10.1016/j.addr.2016.08.004.

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7

Sago, Cory D., Melissa P. Lokugamage, Kalina Paunovska, Daryll A. Vanover, Christopher M. Monaco, Nirav N. Shah, Marielena Gamboa Castro, et al. "High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing." Proceedings of the National Academy of Sciences 115, no. 42 (October 1, 2018): E9944—E9952. http://dx.doi.org/10.1073/pnas.1811276115.

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Dysfunctional endothelium causes more disease than any other cell type. Systemically administered RNA delivery to nonliver tissues remains challenging, in large part because there is no high-throughput method to identify nanoparticles that deliver functional mRNA to cells in vivo. Here we report a system capable of simultaneously quantifying how >100 lipid nanoparticles (LNPs) deliver mRNA that is translated into functional protein. Using this system (named FIND), we measured how >250 LNPs delivered mRNA to multiple cell types in vivo and identified 7C2 and 7C3, two LNPs that efficiently deliver siRNA, single-guide RNA (sgRNA), and mRNA to endothelial cells. The 7C3 delivered Cas9 mRNA and sgRNA to splenic endothelial cells as efficiently as hepatocytes, distinguishing it from LNPs that deliver Cas9 mRNA and sgRNA to hepatocytes more than other cell types. These data demonstrate that FIND can identify nanoparticles with novel tropisms in vivo.

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8

Stone, Shane, Tatjana Heinrich, Suzy Juraja, Jiulia Satiaputra, Clinton Hall, Mark Anastasas, Anna Mills та ін. "β-Lactamase Tools for Establishing Cell Internalization and Cytosolic Delivery of Cell Penetrating Peptides". Biomolecules 8, № 3 (11 липня 2018): 51. http://dx.doi.org/10.3390/biom8030051.

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The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a functional biological molecule comparable in size to many protein therapeutics. The first assay focuses on the delivery of full-length β-lactamase to evaluate the internalization potential of a CPP sequence. The second assay uses a split-protein system where one component of β-lactamase is constitutively expressed in the cytoplasm of a stable cell line and the other component is delivered by a CPP. The delivery of a split β-lactamase component evaluates the cytosolic delivery capacity of a CPP. We demonstrate that these assays are rapid, flexible and have potential for use with any cell type and CPP sequence. Both assays are validated using canonical and novel CPPs, with limits of detection from <500 nM to 1 µM. Together, the β-lactamase assays provide compatible tools for functional characterization of CPP activity and the delivery of biological cargos into cells.

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9

Schwarz, Carsten, Claudio Procaccianti, Laura Costa, Riccardo Brini, Richard Friend, Grazia Caivano, Hosein Sadafi, et al. "Differential Performance and Lung Deposition of Levofloxacin with Different Nebulisers Used in Cystic Fibrosis." International Journal of Molecular Sciences 23, no. 17 (August 24, 2022): 9597. http://dx.doi.org/10.3390/ijms23179597.

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We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the approved nebuliser Zirela. The delivered dose, delivery rate, and aerosol particle size distribution (APSD) for each device were determined using the methods described in the Pharmacopeia. High-resolution computed tomography scans obtained from seven adult patients with mild CF were used to generate computer-aided, three-dimensional models of their airway tree to assess lung deposition using functional respiratory imaging (FRI). The eFlow rapid and the LC Plus showed poor delivery efficiencies due to their high residual volumes. The I-Neb, which only delivers aerosols during the inspiratory phase, achieved the highest aerosol delivery efficiency. However, the I-Neb showed the largest particle size and lowest delivery rate (2.9 mg/min), which were respectively associated with a high extrathoracic deposition and extremely long nebulisation times (>20 min). Zirela showed the best performance considering delivery efficiency (159.6 mg out of a nominal dose of 240 mg), delivery rate (43.5 mg/min), and lung deposition (20% of the nominal dose), requiring less than 5 min to deliver a full dose of levofloxacin. The present study supports the use of drug-specific nebulisers and discourages the off-label use of general-purpose devices with the present levofloxacin formulation since subtherapeutic lung doses and long nebulisation times may compromise treatment efficacy and adherence.

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10

Arnold, Amy E., Laura J. Smith, Greg Beilhartz, Laura C. Bahlmann, Emma Jameson, Roman Melnyk, and Molly S. Shoichet. "Attenuated diphtheria toxin mediates siRNA delivery." Science Advances 6, no. 18 (May 2020): eaaz4848. http://dx.doi.org/10.1126/sciadv.aaz4848.

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Toxins efficiently deliver cargo to cells by binding to cell surface ligands, initiating endocytosis, and escaping the endolysosomal pathway into the cytoplasm. We took advantage of this delivery pathway by conjugating an attenuated diphtheria toxin to siRNA, thereby achieving gene downregulation in patient-derived glioblastoma cells. We delivered siRNA against integrin-β1 (ITGB1)—a gene that promotes invasion and metastasis—and siRNA against eukaryotic translation initiation factor 3 subunit b (eIF-3b)—a survival gene. We demonstrated mRNA downregulation of both genes and the corresponding functional outcomes: knockdown of ITGB1 led to a significant inhibition of invasion, shown with an innovative 3D hydrogel model; and knockdown of eIF-3b resulted in significant cell death. This is the first example of diphtheria toxin being used to deliver siRNAs, and the first time a toxin-based siRNA delivery strategy has been shown to induce relevant genotypic and phenotypic effects in cancer cells.

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11

Jun Loh, Xian, and Tung-Chun Lee. "Gene Delivery by Functional Inorganic Nanocarriers." Recent Patents on DNA & Gene Sequences 6, no. 2 (June 1, 2012): 108–14. http://dx.doi.org/10.2174/187221512801327361.

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12

Qiao, Ruirui. "Functional Polymeric Nanoparticles for Drug Delivery." Current Pharmaceutical Design 28, no. 5 (February 2022): 339. http://dx.doi.org/10.2174/138161282805220111142951.

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13

Jeon, Gumhye, Seung Yun Yang, and Jin Kon Kim. "Functional nanoporous membranes for drug delivery." Journal of Materials Chemistry 22, no. 30 (2012): 14814. http://dx.doi.org/10.1039/c2jm32430j.

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14

Lian, Zheng, and Tianjiao Ji. "Functional peptide-based drug delivery systems." Journal of Materials Chemistry B 8, no. 31 (2020): 6517–29. http://dx.doi.org/10.1039/d0tb00713g.

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15

Paleos, Constantinos M., Leto-Aikaterini Tziveleka, Zili Sideratou, and Dimitris Tsiourvas. "Gene delivery using functional dendritic polymers." Expert Opinion on Drug Delivery 6, no. 1 (January 2009): 27–38. http://dx.doi.org/10.1517/17425240802607345.

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16

Heath, Nikki, Xabier Osteikoetxea, Taiana Mia de Oliveria, Elisa Lázaro-Ibáñez, Olga Shatnyeva, Christina Schindler, Natalie Tigue, et al. "Endosomal escape enhancing compounds facilitate functional delivery of extracellular vesicle cargo." Nanomedicine 14, no. 21 (November 2019): 2799–814. http://dx.doi.org/10.2217/nnm-2019-0061.

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Aim: Extracellular vesicles (EVs) are desirable delivery vehicles for therapeutic cargoes. We aimed to load EVs with Cre recombinase protein and determine whether functional delivery to cells could be improved by using endosomal escape enhancing compounds. Materials & methods: Overexpressed CreFRB protein was actively loaded into EVs by rapalog-induced dimerization to CD81FKBP, or passively loaded by overexpression in the absence of rapalog. Functional delivery of CreFRB was analysed using a HEK293 Cre reporter cell line in the absence and presence of endosomal escape enhancing compounds. Results: The EVs loaded with CreFRB by both active and passive mechanisms were able to deliver functional CreFRB to recipient cells only in the presence of endosomal escape enhancing compounds chloroquine and UNC10217832A. Conclusion: The use of endosomal escape enhancing compounds in conjunction with EVs loaded with therapeutic cargoes may improve efficacy of future EV based therapeutics.

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17

Yuan, Ahu, Yiqiao Hu, and Xin Ming. "Dendrimer conjugates for light-activated delivery of antisense oligonucleotides." RSC Advances 5, no. 44 (2015): 35195–200. http://dx.doi.org/10.1039/c5ra04091d.

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PAMAM dendrimer conjugates are used to co-deliver oligonucleotides and photosensitizers to cancer cells. After photo-irradiation, substantial reporter eGFP expression is produced by functional delivery of a model oligonucleotide.

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18

Parke, Barbara, Richard D. Penn, Suzanne M. Savoy, and Daniel Corcos. "Functional Outcome after Delivery of Intrathecal Baclofen." Archives of Physical Medicine and Rehabilitation 70, no. 1 (January 1989): 30–32. http://dx.doi.org/10.1016/s0003-9993(21)01642-7.

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19

Pegtel, D. M., K. Cosmopoulos, D. A. Thorley-Lawson, M. A. J. van Eijndhoven, E. S. Hopmans, J. L. Lindenberg, T. D. de Gruijl, T. Wurdinger, and J. M. Middeldorp. "Functional delivery of viral miRNAs via exosomes." Proceedings of the National Academy of Sciences 107, no. 14 (March 18, 2010): 6328–33. http://dx.doi.org/10.1073/pnas.0914843107.

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20

Brodin, Jeffrey D., Anthony J. Sprangers, Janet R. McMillan, and Chad A. Mirkin. "DNA-Mediated Cellular Delivery of Functional Enzymes." Journal of the American Chemical Society 137, no. 47 (November 20, 2015): 14838–41. http://dx.doi.org/10.1021/jacs.5b09711.

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21

Xing, Ruijun, Gang Liu, Qimeng Quan, Ashwinkumar Bhirde, Guofeng Zhang, Albert Jin, L. Henry Bryant, et al. "Functional MnO nanoclusters for efficient siRNA delivery." Chemical Communications 47, no. 44 (2011): 12152. http://dx.doi.org/10.1039/c1cc15408g.

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22

Ye, Yuanfeng, Xincheng Mao, Jialing Xu, Jingyang Kong, and Xiaohong Hu. "Functional Graphene Oxide Nanocarriers for Drug Delivery." International Journal of Polymer Science 2019 (January 31, 2019): 1–7. http://dx.doi.org/10.1155/2019/8453493.

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The family of graphene has attracted increasing attention on account of their large specific surface area and good mechanical properties in the biomedical field. However, some characteristics like targeted delivery property and drug delivery capacity could not satisfy the need of a drug carrier. Herein, a graphene oxide (GO) nanocarrier was designed by modification of a folic acid (FA) derivative and a β-cyclodextrin (β-CD) derivative in order to improve two properties, respectively. In the first step, reactive or crosslinkable FA and aldehydic β-CD (β-CD-CHO) were designed and synthesized for further modification. In the second step, synthesized functional molecules were coupled onto GO sheets one by one to obtain the GO nanocarrier. IR spectra and XRD results were used to identify the chemical and structural information before and after modification for the GO nanocarrier. The final GO nanocarrier exhibited a typical thin wrinkled sheet morphology of the GO sheet without any influence by two functional molecules. Finally, in vitro evaluation was used to clarify the drug loading and controlling capacity of the nanocarrier as a drug delivery system. The results revealed that the GO nanocarrier had a better CPT loading capacity and showed better controllability for CPT release.

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23

Tezgel, A. Özgül, Paejonette Jacobs, Coralie M. Backlund, Janice C. Telfer, and Gregory N. Tew. "Synthetic Protein Mimics for Functional Protein Delivery." Biomacromolecules 18, no. 3 (February 27, 2017): 819–25. http://dx.doi.org/10.1021/acs.biomac.6b01685.

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24

Constantinescu, Florin-Eugen. "Functional Biomaterials Drug Delivery and Biomedical Applications." STOMATOLOGY EDU JOURNAL 9, no. 3-4 (2022): 133. http://dx.doi.org/10.25241/stomaeduj.2022.9(3-4).bookreview.5.

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25

Patil, Gao, Lin, Li, Dang, Tian, Zhang, Jiang, Qadir, and Qian. "The Development of Functional Non-Viral Vectors for Gene Delivery." International Journal of Molecular Sciences 20, no. 21 (November 4, 2019): 5491. http://dx.doi.org/10.3390/ijms20215491.

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Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

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26

Feng, Yiming, and Youngsoo Lee. "Microfluidic assembly of food-grade delivery systems: Toward functional delivery structure design." Trends in Food Science & Technology 86 (April 2019): 465–78. http://dx.doi.org/10.1016/j.tifs.2019.02.054.

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27

Ruan, Jinglin, and Volker Patzel. "Abstract P23: Mitochondrial Delivery of Functional Nucleic Acids for Targeting of Mitochondrial Dysfunction." Cancer Research 84, no. 8_Supplement (April 15, 2024): P23. http://dx.doi.org/10.1158/1538-7445.fcs2023-p23.

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Abstract Mitochondria is the main power supply for cellular activity and a key player for the regulation of cellular metabolism, and they contain their own DNA. Critical proteins for mitochondrial functions are not only encoded by nuclear DNA (nDNA) but also by mitochondrial DNA (mtDNA). Abnormalities in mitochondrial functions could lead to diseases including neurodegeneration, diabetes, and cancer progression. The ability for a non-coding RNA (β2.7) of human cytomegalovirus (CMV) to localize to the host mitochondria revealed its potential to be used as a tool for mitochondria gene targeting. Using computational methods, our lab identified four thermodynamically conserved structural subdomains (D1 to D4) within the β2.7 RNA. While all four domains exhibited mitochondrial uptake potential, sub-domain D3 exhibited the highest absolute mitochondrial targeting activity and sub-domain D2 the highest activity per nucleotide. Further modifications on different sub-domain alignments found that maximum uptake efficiency was achieved by tandem repeats of 4 copies of D3 domains followed by 4 copies of D2 domains (abbreviated as D3 × 4_D2 × 4). Delivery of a GFP-coding mRNA or antisense RNA targeting mitochondrial genes mt-ATP6 and mt-ATP8 both confirmed its ability to co-deliver functional RNA into mitochondria. To cleave and destroy mutated mitochondrial genomes for future gene therapeutic applications, we explore mitochondrial delivery of the CRISPR-Cas9 system. The mRNAs coding for the wild-type Cas9 as well as more specific Cas9 variants were fused to the mitochondrial delivery vector (D3 × 4_D2 × 4). Latest RT-qPCR on mitochondrial RNA showed delivery of Cas9 mRNA into mitochondria of HepG2 cells. Currently, we investigate co-delivery of single-guide RNA and quantify Cas9 expression in mitochondria. In an alternative approach we deliver sequences coding for functional mitochondrial protein. Examples are the mRNAs coding for mitochondrial proteins mt-ND1, -ND4 or -ND6 which are frequently mutated is patients with Leber’s hereditary optic neuropathy (LHON). Citation Format: Jinglin Ruan, Volker Patzel. Mitochondrial Delivery of Functional Nucleic Acids for Targeting of Mitochondrial Dysfunction [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P23.

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28

Booth, Michael J., Vanessa Restrepo Schild, Florence G. Downs, and Hagan Bayley. "Functional aqueous droplet networks." Molecular BioSystems 13, no. 9 (2017): 1658–91. http://dx.doi.org/10.1039/c7mb00192d.

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29

Anitha, P., J. Bhargavi, G. Sravani, B. Aruna, and Ramkanth S. "RECENT PROGRESS OF DENDRIMERS IN DRUG DELIVERY FOR CANCER THERAPY." International Journal of Applied Pharmaceutics 10, no. 5 (September 8, 2018): 34. http://dx.doi.org/10.22159/ijap.2018v10i5.27075.

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With the recent advances of nanotechnology, dendrimers are emerging as a highly attractive class of drug delivery vectors for cancer therapy. Dendrimers are multifunctional smart Nanocarriers to deliver one or more therapeutic agent safely and selectively to cancer cells. The high level of control over the synthesis of dendritic architecture makes dendrimers a nearly perfect (spherical) nanocarrier for site-specific drug delivery. The presence of functional groups in the dendrimers exterior also permits the addition of other moieties that can actively target certain diseases which are now widely used as tumor targeting strategies. Drug encapsulation, solubilization and passive targeting also equally contribute to the therapeutic use of dendrimers. Dendrimers are ideal carrier vehicles on cytotoxicity, blood plasma retention time, biodistribution and tumor uptake. In this review we highlight the advantages of dendrimers over conventional chemotherapy, toxicity and its management, following anti-cancer drugs delivered by using dendrimers and recent advances in drug delivery by various types of dendrimers as well as its diagnostic applications.

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30

McKinlay, Colin J., Jessica R. Vargas, Timothy R. Blake, Jonathan W. Hardy, Masamitsu Kanada, Christopher H. Contag, Paul A. Wender, and Robert M. Waymouth. "Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals." Proceedings of the National Academy of Sciences 114, no. 4 (January 9, 2017): E448—E456. http://dx.doi.org/10.1073/pnas.1614193114.

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Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(α-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.

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31

Yu, Xueliang, Shuai Liu, Qiang Cheng, Sang M. Lee, Tuo Wei, Di Zhang, Lukas Farbiak, Lindsay T. Johnson, Xu Wang, and Daniel John Siegwart. "Hydrophobic Optimization of Functional Poly(TPAE-co-suberoyl chloride) for Extrahepatic mRNA Delivery following Intravenous Administration." Pharmaceutics 13, no. 11 (November 12, 2021): 1914. http://dx.doi.org/10.3390/pharmaceutics13111914.

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Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared to other nucleic acids (e.g., siRNA and pDNA), there are more opportunities to improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library of 1200 functional polyesters for systemic mRNA delivery. We focused on the chemical investigation of hydrophobic optimization as a method to adjust mRNA polyplex stability, diameter, pKa, and efficacy. Focusing on a region of the library heatmap (PE4K-A17), we further explored the delivery of luciferase mRNA to IGROV1 ovarian cancer cells in vitro and to C57BL/6 mice in vivo following intravenous administration. PE4K-A17-0.2C8 was identified as an efficacious carrier for delivering mRNA to mouse lungs. The delivery selectivity between organs (lungs versus spleen) was found to be tunable through chemical modification of polyesters (both alkyl chain length and molar ratio in the formulation). Cre recombinase mRNA was delivered to the Lox-stop-lox tdTomato mouse model to study potential application in gene editing. Overall, we identified a series of polymer-mRNA polyplexes stabilized with Pluronic F-127 for safe and effective delivery to mouse lungs and spleens. Structure–activity relationships between alkyl side chains and in vivo delivery were elucidated, which may be informative for the continued development of polymer-based mRNA delivery.

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Sellers, Drew L., Jamie M. Bergen, Russell N. Johnson, Heidi Back, John M. Ravits, Philip J. Horner, and Suzie H. Pun. "Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration." Proceedings of the National Academy of Sciences 113, no. 9 (February 17, 2016): 2514–19. http://dx.doi.org/10.1073/pnas.1515526113.

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A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics.

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Rezvani, Mohaddeseh, Narmin Ghani Zadeh Hesar, Ebrahim Mohammad Ali Nasab Firouzjah, and Hengameh Sheikh. "Comparing Functional Disability and Body Image Between Women With Normal Delivery and Cesarean Section." Scientific Journal of Rehabilitation Medicine 13, no. 03 (July 1, 2024): 650–63. http://dx.doi.org/10.32598/sjrm.13.3.3156.

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Background and Aims During pregnancy, a woman’s body undergoes many changes, which can be studied from physiological and psychological aspects. The purpose of this research is to compare functional disability and body image after normal and cesarean delivery. Methods The current research is of a comparative causal type. In this study, 114 non-athlete women who gave birth in Urmia City, Iran, were selected voluntarily and availably within one month after delivery. Of these, 58 had a normal delivery and 56 a cesarean delivery. Back functional disability was evaluated by the Oswestry disability index questionnaire, knee functional disability by the international knee documentation committee questionnaire, and body image by body image questionnaire in pregnant women. The data were analyzed using SPSS software, version 24. Results The independent t test showed a significant difference between the functional disability of the back and knees in the two groups with normal delivery and cesarean delivery. So, the cesarean section group had more disability in the low back and knee area compared to the normal delivery group (P=0.001). Also, the normal delivery group had a better body image compared to the cesarean group. Conclusion Normal delivery can be considered a safe delivery method to prevent the occurrence of functional disability in the back and knees and effectively reduce adverse symptoms related to body image after delivery.

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Lee, Eun-Seong, Ji-Hoon Kim, Jeong-Min Yun, Kyung-Soo Lee, Ga-Young Park, Beom-Jin Lee, and Kyung-Taek Oh. "Functional Polymers for Drug Delivery Systems in Nanomedicines." Journal of Pharmaceutical Investigation 40, spc (May 15, 2010): 45–61. http://dx.doi.org/10.4333/kps.2010.40.s.045.

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Agrawal, Amit, Dal-Hee Min, Neetu Singh, Haihao Zhu, Alona Birjiniuk, Geoffrey von Maltzahn, Todd J. Harris, et al. "Functional Delivery of siRNA in Mice Using Dendriworms." ACS Nano 3, no. 9 (August 12, 2009): 2495–504. http://dx.doi.org/10.1021/nn900201e.

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Norton, J. E., Y. Gonzalez Espinosa, R. L. Watson, F. Spyropoulos, and I. T. Norton. "Functional food microstructures for macronutrient release and delivery." Food & Function 6, no. 3 (2015): 663–78. http://dx.doi.org/10.1039/c4fo00965g.

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There is a need to understand the role of fat, protein and carbohydrate in human health, and also how foods containing and/or structured using these macronutrients can be designed so that they can have a positive impact on health.

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Mendes, Rafael G., Alicja Bachmatiuk, Bernd Büchner, Gianaurelio Cuniberti, and Mark H. Rümmeli. "Carbon nanostructures as multi-functional drug delivery platforms." J. Mater. Chem. B 1, no. 4 (2013): 401–28. http://dx.doi.org/10.1039/c2tb00085g.

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Lee, M. C., and D. K. Menon. "Sublingual drug delivery during functional magnetic resonance imaging." Anaesthesia 60, no. 8 (August 2005): 821–22. http://dx.doi.org/10.1111/j.1365-2044.2005.04307.x.

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Hawiger, Jacek. "Noninvasive intracellular delivery of functional peptides and proteins." Current Opinion in Chemical Biology 3, no. 1 (February 1999): 89–94. http://dx.doi.org/10.1016/s1367-5931(99)80016-7.

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Ding, Jianxun, and Xuesi Chen. "Functional polymer nanocarriers for rational antitumor drug delivery." Nanomedicine: Nanotechnology, Biology and Medicine 14, no. 5 (July 2018): 1875–76. http://dx.doi.org/10.1016/j.nano.2017.11.359.

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Barclay, Thomas G., Candace Minhthu Day, Nikolai Petrovsky, and Sanjay Garg. "Review of polysaccharide particle-based functional drug delivery." Carbohydrate Polymers 221 (October 2019): 94–112. http://dx.doi.org/10.1016/j.carbpol.2019.05.067.

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Liu, Gang, Magdalena Swierczewska, Seulki Lee, and Xiaoyuan Chen. "Functional nanoparticles for molecular imaging guided gene delivery." Nano Today 5, no. 6 (December 2010): 524–39. http://dx.doi.org/10.1016/j.nantod.2010.10.005.

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Sun, Wenchao, Mohammed Inayathullah, Martin A. C. Manoukian, Andrey V. Malkovskiy, Sathish Manickam, M. Peter Marinkovich, Alfred T. Lane, Lobat Tayebi, Alexander M. Seifalian, and Jayakumar Rajadas. "Transdermal Delivery of Functional Collagen Via Polyvinylpyrrolidone Microneedles." Annals of Biomedical Engineering 43, no. 12 (June 12, 2015): 2978–90. http://dx.doi.org/10.1007/s10439-015-1353-0.

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Tila, Dena, Saeed Ghasemi, Seyedeh Narjes Yazdani-Arazi, and Saeed Ghanbarzadeh. "Functional liposomes in the cancer-targeted drug delivery." Journal of Biomaterials Applications 30, no. 1 (March 29, 2015): 3–16. http://dx.doi.org/10.1177/0885328215578111.

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Babikova, Dimitrina, Radostina Kalinova, Ivelina Zhelezova, Denitsa Momekova, Spiro Konstantinov, Georgi Momekov, and Ivaylo Dimitrov. "Functional block copolymer nanocarriers for anticancer drug delivery." RSC Advances 6, no. 88 (2016): 84634–44. http://dx.doi.org/10.1039/c6ra19236j.

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Hasadsri, Linda, Jörg Kreuter, Hiroaki Hattori, Tadao Iwasaki, and Julia M. George. "Functional Protein Delivery into Neurons Using Polymeric Nanoparticles." Journal of Biological Chemistry 284, no. 11 (January 7, 2009): 6972–81. http://dx.doi.org/10.1074/jbc.m805956200.

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Kulkarni, Abhijeet D., Aditya A. Joshi, Chirag L. Patil, Prasad D. Amale, Harun M. Patel, Sanjay J. Surana, Veena S. Belgamwar, Kapil S. Chaudhari, and Chandrakantsing V. Pardeshi. "Xyloglucan: A functional biomacromolecule for drug delivery applications." International Journal of Biological Macromolecules 104 (November 2017): 799–812. http://dx.doi.org/10.1016/j.ijbiomac.2017.06.088.

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Laus, M., K. Sparnacci, M. Lelli, R. Vannini, and L. Tondelli. "Core-shell functional nanospheres for oligonucleotide delivery. II." Journal of Polymer Science Part A: Polymer Chemistry 38, no. 7 (April 1, 2000): 1110–17. http://dx.doi.org/10.1002/(sici)1099-0518(20000401)38:7<1110::aid-pola8>3.0.co;2-5.

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Cezar, Christine A., Praveen Arany, Sarah A. Vermillion, Bo Ri Seo, Herman H. Vandenburgh, and David J. Mooney. "Timed Delivery of Therapy Enhances Functional Muscle Regeneration." Advanced Healthcare Materials 6, no. 19 (July 13, 2017): 1700202. http://dx.doi.org/10.1002/adhm.201700202.

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Tripodo, G., D. Mandracchia, R. Dorati, A. Latrofa, I. Genta, and B. Conti. "Nanostructured Polymeric Functional Micelles for Drug Delivery Applications." Macromolecular Symposia 334, no. 1 (December 2013): 17–23. http://dx.doi.org/10.1002/masy.201300099.

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