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Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

ABSTRACT: Exosomes are small membranous vesicles implicated in intercellular signalling. Through their uncanny ability to carry and deliver donor cellular cargo (biomolecules) to target cells, they exert a profound effect on the regular functioning of healthy cells and play a significant role in pathogenesis and progression of several diseases, including cancer. The composition and number of endogenously circulating exosomes frequently vary, which is often reflective of the pathophysiological status of the cell. Applicability of exosomes derived from normal cells as a drug carrier with or without modifying their intraluminal and surface components are generally tested. Conversely, exosomes also are reported to contribute to resistance towards several anti-cancer therapies. Therefore, it is necessary to carefully evaluate the role of exosomes in cancer progression, resistance and the potential use of exosomes as a delivery vehicle of cancer therapeutics. In this review, we summarize the recent advancements in the exploitation of exosomes as a drug delivery vehicle. We also discuss the role of exosomes in conferring resistance to anti-cancer therapeutics. While this review is focused on cancer, the exosome-based drug delivery and resistance is also applicable to other human diseases.

SUBMITTER: Chinnappan M

PROVIDER: S-EPMC7327711 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

Chinnappan Mahendran M Srivastava Akhil A Amreddy Narsireddy N Razaq Mohammad M Pareek Vipul V Ahmed Rebaz R Mehta Meghna M Peterson Jo Elle JE Munshi Anupama A Ramesh Rajagopal R

Cancer letters 20200519

Exosomes are small membranous vesicles implicated in intercellular signalling. Through their uncanny ability to carry and deliver donor cellular cargo (biomolecules) to target cells, they exert a profound effect on the regular functioning of healthy cells and play a significant role in pathogenesis and progression of several diseases, including cancer. The composition and number of endogenously circulating exosomes frequently vary, which is often reflective of the pathophysiological status of th ...[more]

PMID: 32439419

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Project description:In recent decades, drug delivery systems (DDSs) based on polymer nanoparticles have been explored due to their potential to deliver drugs with poor water solubility. Some of the limitations of nanoparticle-based DDSs can be overcome by developing an appropriate polymer prodrug. In this work, poly(NIPA)-b-poly(HMNPPA)-b-poly(PEGMA-stat-BA) was synthesized using reversible addition fragmentation chain transfer polymerization and Chlorambucil (Cbl), an anticancer drug, was conjugated to the copolymer via 3-(3-(hydroxymethyl)-4-nitrophenoxy)propyl acrylate (HMNPPA) units to prepare the prodrug. A few biotin acrylate (BA) units were also incorporated to bring potential targeting capability to the prodrug in the copolymer. This polymer prodrug formed spherical micellar nanoparticles in physiological conditions, which were characterized by dynamic light scattering and transmission electron microscopy measurements. The very low critical aggregation concentration (cac) (0.011 mg/mL) of the prodrug, as measured from Nile Red fluorescence, makes it stable against dilution. The polymer prodrug was shown to release Cbl on photoirradiation by soft UV (λ ≥ 365 nm) and laser (λ = 405 nm) light. The prodrug micellar nanoparticles were capable of encapsulating a second drug (doxorubicin, DOX) in their hydrophobic core. On photoirradiation with UV and laser light of the DOX-loaded nanoparticles, both Cbl and DOX were released. Light-induced breaking of photolabile ester bond resulted in the release of Cbl and caused disruption of the nanoparticles facilitating release of DOX. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed the nontoxicity of the polymers and effectiveness of the dual drug-loaded micellar nanoparticles toward cancer cells. Confocal microscopy results showed a better cellular internalization capability of the DOX-loaded nanoparticles in cancer cells, possibly due to the presence of cancer cell targeting biotin molecules in the polymer. This new photoresponsive potentially biocompatible and cancer cell-targeted polymer prodrug may be useful for delivery of single and/or multiple hydrophobic drugs.

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Dataset Information

Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

Publications

Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

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