Premium
Stimuli‐responsive nanoparticles for the codelivery of chemotherapeutic agents doxorubicin and siPD‐L1 to enhance the antitumor effect
Author(s) -
Zhou Yejuan,
Wan Wenjun,
Tong Yao,
Chen Mengtian,
Wang Dandan,
Wang Yu,
You Bengang,
Liu Yang,
Zhang Xueg
Publication year - 2020
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.34516
Subject(s) - doxorubicin , materials science , gene silencing , in vivo , cancer research , small interfering rna , cancer cell , cancer , chemotherapy , pharmacology , transfection , chemistry , biology , biochemistry , gene , microbiology and biotechnology , genetics
Cancer cells have been reported to exhibit high resistance against immune system recognition through various cell intrinsic and extrinsic mechanisms. Considerable challenges have been encountered in monotherapy with chemotherapeutics to attain the desired antitumor efficacy. In this study, a nanodelivery system was designed to incorporate doxorubicin (DOX) and programmed death‐ligand 1 (PD‐L1) small interfering RNA (siRNA), that is, siPD‐L1. DOX and siPD‐L1 were formed from a stimuli‐responsive polymer with a poly‐L‐lysine–lipoic acid reduction‐sensitive core and a tumor extracellular pH‐stimulated shedding polyethylene glycol layer. The codelivery system was stable under physiological pH conditions and demonstrated enhanced cellular uptake at the tumor site. Moreover, the combined treatment of DOX and siPD‐L1 exhibited improved antitumor effect in vitro and in vivo compared with either modality alone. The combination of chemotherapy and immunotherapy presented in this work through the codelivery of a chemotherapeutic agent and a gene‐silencing agent (siRNA) may provide a new strategy for cancer treatment.