Copper sulfide engineered covalent organic frameworks for pH-responsive chemo/photothermal/chemodynamic synergistic therapy against cancer

Developing nanomedicines with high-performance is a promising therapeutic strategy for cancer treatment. Herein, a multifunctional nanoplatform (CuS@COFs-BSA-FA/DOX) based on copper sulfide nanoparticles engineered covalent organic frameworks (CuS@COFs) has been established for synergistic photothermal therapy (PTT), chemotherapy and chemodynamic therapy (CDT). The high photothermal effect and excellent Fenton-like catalytic activity enabled CuS@COFs to generate a new minimally invasive PTT/CDT synergistic therapy. Moreover, with the pH-dependent fluorescence behavior and the inherited mesoporous structure, the nanocomposites can also be utilized as fluorescent probes for cancer cell imaging and drug-delivery carriers to encapsulate the chemotherapeutic agent, DOX. The densely coated PEI and BSA-FA layers on the surface of CuS@COFs not only increased the cancer-targeting efficiency but also prevented the nonspecific release of DOX from CuS@COFs. The acid tumor microenvironment and near-infrared light triggered the release of DOX for chemotherapy, which simultaneously augmented the CDT efficiency of CuS@COFs. Notably, the localized hyperthermia induced by PTT can further improve the CDT efficiency of the nanoplatform, leading to a synergistic PTT/chemotherapy/CDT effect. The nanoplatform possessed the capability of cancer cell-targeted imaging and achieved better therapeutic efficacy with negligible systemic toxicity both in vitro and in vivo. Our work opens up a powerful avenue for developing multifunctional COFs-based theranostic platform and shows strong potential in practical applications.