Near-infrared light-triggered synergistic antitumor therapy based on hollow ZIF-67-derived Co3S4-indocyanine green nanocomplex as a superior reactive oxygen species generator

Abstract

Reactive oxygen species (ROS) with strong oxidability have been considered as effective agents for antitumor therapy through oxidative damage to lipids, proteins, DNA and RNA. In this work, a multifunctional hollow cobaltosic sulfide (Co₃S₄)/photosensitizer indocyanine green (ICG) nanocomplex (Co₃S₄-ICG) has been synthesized by efficiently loading ICG into the hollow Co₃S₄ to realize synergistic antitumor therapy via chemodynamic therapy (CDT), photodynamic therapy (PDT) and photothermal therapy (PTT) under near-infrared (808 nm) laser irradiation. Co₃S₄ nanoparticles would be degraded in tumor acidic microenvironment into Co²⁺, which locally triggers a Fenton-like reaction to produce cytotoxic hydroxyl radicals (OH) for CDT. Co₃S₄-ICG could also produce singlet oxygen (¹O₂) through a multi-step photochemical process for PDT under 808 nm laser irradiation. The slow release of ICG in the tumor region was achieved due to hollow-structured Co₃S₄ working as nanocarriers, and which has been proved an effective approach for combined CDT/PDT. In addition, Co₃S₄-ICG showed high photothermal conversion efficiency (40.5%) for PTT, and excellent OH generation capability via photothermal-improved Fenton reaction, leading to the synergistically improved antitumor efficacy. In vitro and in vivo experimental results confirm that the combined PTT/PDT/photothermal-enhanced CDT therapy can effectively ablate tumors with a negligible systemic toxicity. This work provides a valuable strategy for designing and constructing of a multifunctional nanoplatform for synergistic antitumor therapy of solid tumors.

Keywords: Fenton-like reaction; Hollow structured Co(3)S(4)-ICG; ROS generator; Synergetic antitumor therapy; Tumor microenvironment-responsive.