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Preparation of pH- and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly

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Abstract

pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P (DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA-co-CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/ hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2017YFA0205601) and the National Natural Science Foundation of China (51625305, 21704095, 21774113, 21525420).

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Authors and Affiliations

  1. CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Miao Chen, Jia-Wei Li, Chun-Yan Hong, Wen-Jian Zhang & Ye-Zi You

  2. The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China

    Wei-Guo Zhang

Authors
  1. Miao Chen
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  2. Wei-Guo Zhang
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  3. Jia-Wei Li
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  4. Chun-Yan Hong
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  5. Wen-Jian Zhang
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  6. Ye-Zi You
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Correspondence to Wen-Jian Zhang or Ye-Zi You.

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Chen, M., Zhang, WG., Li, JW. et al. Preparation of pH- and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly. Sci. China Chem. 61, 1159–1166 (2018). https://doi.org/10.1007/s11426-018-9268-y

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  • DOI: https://doi.org/10.1007/s11426-018-9268-y

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