Zwitterionic polypeptide nanomedicine with dual NIR/reduction-responsivity for synergistic cancer photothermal-chemotherapy

Abstract

The zwitterionic polypeptides with clinically-relevant stimuli-responsivity hold great potential for advanced drug delivery systems and cancer therapy. Herein, we synthesized the phosphorylcholine- and thiol-pendant polypeptide (PMC) and constructed a novel kind of dual NIR/reduction-responsive and zwitterionic polypeptide nanoparticle (i.e., PMC/DOX-ICG) for simultaneous co-delivery of doxorubicin (DOX) and indocyanine green (ICG), which integrated chemotherapy (CT), photothermal therapy (PTT), and NIR fluorescence imaging together. The zwitterionic polypeptide nanoparticles of PMC/DOX-ICG exhibited great stability in 10% fetal bovine serum, good photothermal properties, and dual NIR/reduction-responsive DOX release profiles. The combination PTT-CT based on PMC/DOX-ICG plus mild NIR irradiation (808 nm, 1 W cm⁻², 10 min) produced a synergistic antitumor efficacy, in which the zwitterionic polypeptide nanoparticles and photothermia cooperatively assisted to transport DOX and ICG inside the HeLa cells, as confirmed by means of MTT assay, CLSM, and flow cytometry. In vivo NIR fluorescence and photothermal imaging and the biodistribution analysis demonstrate that PMC/DOX-ICG induced a preferable tumor accumulation effect, and the ICG level in the tumor increased 10.7-fold compared to the control. Importantly, by using one dose of PMC/DOX-ICG and a single dose of NIR irradiation, the PTT-CT treatment completely eradicated the HeLa tumors without recurrence in 30 days while the single PTT or CT only lowered the tumor growth rate, exhibiting superior and synergistic antitumor efficacy in vivo.