ab0c00125_si_001.pdf (402.57 kB)
Hypoxia-Responsive Polypeptide Nanoparticles Loaded with Doxorubicin for Breast Cancer Therapy
journal contribution
posted on 2020-03-18, 19:36 authored by Peng Zhang, Huailin Yang, Wei Shen, Wanguo Liu, Li Chen, Chunsheng XiaoMicroenvironments
of various solid tumors are characterized by
hypoxia. Herein, we report a novel nanoparticle that can selectively
release loaded drugs in hypoxic environments. The nanoparticle was
prepared using a hypoxia-responsive amphiphilic polymer in aqueous
media. The polymer was synthesized by conjugating a hydrophobic small
molecule, 4-nitrobenzyl (3-azidopropyl) carbamate, to the side chains
of an mPEG-PPLG copolymer. Doxorubicin (DOX) could be loaded into
the nanoparticles with a high efficiency of 97.8%. The generated drug-loaded
micellar nanoparticles (PPGN@DOX) presented hypoxia-sensitive drug
release behavior in vitro. Meanwhile, PPGN@DOX could be effectively
internalized by 4T1 cells and could release DOX into the cell nuclei
under hypoxic conditions. The in vitro anticancer results suggested
that PPGN@DOX presented superior tumor cell-killing ability compared
with free DOX in hypoxic environments. Furthermore, PPGN@DOX prolonged
the blood circulation time and improved the biological distribution
of DOX, resulting in increased antitumor outcomes and reduced side
effects in vivo. Overall, the present work demonstrates that hypoxia-responsive
nanoparticles have great application potential in the treatment of
hypoxic tumors.