Issue 35, 2020

Photo-induced specific intracellular release EGFR inhibitor from enzyme/ROS-dual sensitive nano-platforms for molecular targeted-photodynamic combinational therapy of non-small cell lung cancer

Abstract

Molecular targeted-photodynamic combinational therapy is a promising strategy to enhance antitumor effects; meanwhile, current nanocarriers face challenges of limited selective delivery and release of therapeutic agents to specific tumor sites, which significantly compromises their therapeutic efficacy. Herein, we report active-targeting, enzyme- and ROS-dual responsive nanoparticles (HPGBCA) consisting of CD44-targeting hyaluronic acid (HA) shells and afatinib (AFT)-loaded, ROS-sensitive poly(L-lysine)-conjugated chlorin e6 (Ce6) derivative nanoparticle cores (PGBCA). HPGBCA can actively carry AFT and Ce6 specifically to tumor cells due to the negatively charged HA and CD44-mediated active targeting. Subsequently, hyaluronidase in the endosome will further spur the degradation of the HA shell to prompt exposure of the positively charged PGBCA core for rapid endosomal escape and intracellular delivery of AFT and Ce6. Furthermore, the generation of ROS produced by Ce6 under NIR irradiation can trigger the rapid oxidation of the thioether linker to facilitate the release of AFT into the cytoplasm. In vitro and in vivo studies demonstrated that the released AFT and excessive ROS at the local site can synergistically induce cell apoptosis to enhance the therapeutic efficacy without side effects. Our developed intelligent nanoparticle provides new avenues to achieve on-demand, specific intracellular drug release for improved molecular targeted-photodynamic combination therapeutic efficacy.

Graphical abstract: Photo-induced specific intracellular release EGFR inhibitor from enzyme/ROS-dual sensitive nano-platforms for molecular targeted-photodynamic combinational therapy of non-small cell lung cancer

Supplementary files

Article information

Article type
Paper
Submitted
22 апр 2020
Accepted
11 юни 2020
First published
11 авг 2020

J. Mater. Chem. B, 2020,8, 7931-7940

Photo-induced specific intracellular release EGFR inhibitor from enzyme/ROS-dual sensitive nano-platforms for molecular targeted-photodynamic combinational therapy of non-small cell lung cancer

M. Zhang, X. Zhang, S. Cai, H. Mei, Y. He, D. Huang, W. Shi, S. Li, J. Cao and B. He, J. Mater. Chem. B, 2020, 8, 7931 DOI: 10.1039/D0TB01053G

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