Amphiphilic Triblock Copolymer Prodrug for Tumor-Specific pH/Reduction Dual-Triggered Drug Delivery: Effect of Self-Assembly Behaviors

Posted on 11.06.2021 - 04:29
Diblock copolymer-based prodrugs have been widely designed for tumor treatment after self-assembly; however, premature drug leakage could not be ignored because their hydrophobic prodrug cores were directly exposed to the media. Here, an amphiphilic triblock copolymer prodrug with a hydrophilic PEG block, a pH-sensitive poly­(2-(diisopropylamino)­ethyl methacrylate) (PDPA) block, and a hydrophobic reduction-cleavable prodrug block was synthesized for tumor-specific pH/reduction dual-triggered drug delivery, via the successive RAFT polymerization of DPA and a DOX-based monomer (MAL-DOX) with a PEG-based macro-CTA. The core–shell and core–shell-corona nanoparticles could be obtained by one-step and two-step self-assembly. With the pH-sensitive gatekeeper formed by the PDPA block, the core–shell-corona nanoparticles possessed a smaller diameter with narrow distribution and better drug release with lower drug leakage. MTT assays demonstrated the selective cytotoxicity of the core–shell-corona nanoparticles to the cancer cells was dose-dependent because of the reduction-cleavable prodrug. The negligible drug leakage and selective cytotoxicity to cancer cells endow the proposed core–shell-corona prodrug nanoparticles with promising potential for tumor treatment without toxic side effects on the normal cells.

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Dong, Yuman; Liu, Peng (1753): Amphiphilic Triblock Copolymer Prodrug for Tumor-Specific pH/Reduction Dual-Triggered Drug Delivery: Effect of Self-Assembly Behaviors. ACS Publications. Collection. https://doi.org/10.1021/acs.langmuir.1c00680
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