Premium
Self‐Assembled Polyprodrug Amphiphile for Subcutaneous Xenograft Tumor Inhibition with Prolonged Acting Time In Vivo
Author(s) -
Chen Dong,
Huang Yu,
Xu Shuting,
Jiang Huangyong,
Wu Jieli,
Jin Xin,
Zhu Xinyuan
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700174
Subject(s) - amphiphile , chemistry , phosphorylcholine , micelle , in vivo , methacrylate , biophysics , raft , drug delivery , polymerization , polymer , combinatorial chemistry , copolymer , organic chemistry , biochemistry , aqueous solution , microbiology and biotechnology , biology
Polymeric drug delivery system termed as “polyprodrug amphiphile” poly(2‐methylacryloyloxyethyl phosphorylcholine)‐ b ‐poly(10‐hydroxy‐camptothecin methacrylate (pMPC‐ b ‐pHCPT) is developed for the prolonged‐acting cancer therapy. It is obtained by two‐step reversible addition–fragmentation chain transfer polymerization of zwitterionic monomer MPC and an esterase‐responsive polymerizable prodrug methacrylic anhydride–CPT, respectively. This diblock polymer is composed of both antifouling (pMPC) and bioactive (pHCPT) segments and the drug is designed as a building block to construct the polymer skeleton directly. Due to its distinct amphiphilicity, the polymer can self‐assemble into micelles with different dynamic sizes by facilely tuning the ratio of MPC/HCPT under physiological conditions. The outer pMPC shell is superhydrophilic to form dense hydrate layer preventing the nanosystem from unwanted nonspecific protein adsorption, which is the main lead cause of the rapid clearance of nanoparticles in vivo, thus facilitating the accumulation of drugs in tumor sites via enhanced permeability and retention effect. The configuration of the polyprodrug amphiphile is confirmed by several measurements. The resistance to albumin adsorption, prolonged plasma retention time, accumulation in tumor sites, and anticancer activity of the micelles is also investigated in vitro and in vivo. This novel amphiphile can be expected as a promising agent for the passive targeted prolonged‐acting cancer therapy.