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- W2904134775 abstract "Maytansine and its related analogues are a class of highly potent anti-proliferation agents that have failed to be exploited as clinical drugs for human therapy due to unacceptable systemic toxicity. Here, we delineate a novel strategy that combines rational drug conjugation with subsequent nanoparticle assembly to systemically deliver this highly potent and toxic drug. To demonstrate this concept, we covalently coupled the thiolated maytansine derivative, the DM1 agent, to amphiphilic block co-polymers, polyethylene glycol (PEG)-block-polylactide (PLA), in varying molecular weights to generate two prodrug constructs (i.e., PEG2K-PLA2K-DM1 and PEG2K-PLA4K-DM1) via the maleimide-thiol reaction. The resulting two constructs are amenable to self-assembly in aqueous solutions and are systemically injectable for preclinical studies. In vivo evaluations indicate that PEG-PLA-DM1 conjugate-assembled nanoparticles (NPs) display substantially reduced drug toxicity compared to the free drug forms and NPs that physically encapsulate DM1. Furthermore, following systemic administration, these nanodrugs produced superior therapeutic efficacy over free DM1 in a colon tumor xenograft-bearing mouse model. Therefore, this study provides evidence that the conjugation of toxic drugs to assembling copolymers enables the alleviation of cancer drug toxicity and effective delivery of anticancer drugs. Thus, this DM1-formulated platform represents a new generation of nanotherapeutics that are available for further clinical evaluation." @default.
- W2904134775 created "2018-12-22" @default.
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- W2904134775 date "2019-02-01" @default.
- W2904134775 modified "2023-10-16" @default.
- W2904134775 title "Revival of a potent therapeutic maytansinoid agent using a strategy that combines covalent drug conjugation with sequential nanoparticle assembly" @default.
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- W2904134775 cites W2030177226 @default.
- W2904134775 cites W2030450209 @default.
- W2904134775 cites W2032815757 @default.
- W2904134775 cites W2039338567 @default.
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- W2904134775 cites W2380635053 @default.
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- W2904134775 doi "https://doi.org/10.1016/j.ijpharm.2018.12.017" @default.
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- W2904134775 hasPublicationYear "2019" @default.
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