Nanoscale covalent organic framework for the low-temperature treatment of tumor growth and lung metastasis

Abstract

Photothermal therapy (PTT) has shown promising applications in tumor therapies. However, due to laser-induced nonspecific heating and heat diffusion, high levels of hyperthermia (>50°C) in tumor tissues often increase the risk of cancer recurrence and metastasis, which causes the patient pain and destroys the surrounding normal cells and tissues. It is therefore important to develop photothermal strategies that have excellent therapeutic efficiencies under low-temperature conditions (≤45°C). In addition, the heterogeneity and complexity of tumors require the development of combinatorial antitumor treatments as the therapeutic efficiency of monomodal PTT is not currently sufficient. Herein, we have adopted a stepwise synthetic approach to develop a highly efficient multimodal therapeutic agent GA@PCOF@PDA by successive bonding defect functionalization (BDF), guest encapsulation, and surface modification steps. The covalently grafted porphyrinic photosensitizers (Por), encapsulated gambogic acid (GA), and surface-modified PDA film are independently responsible for photodynamic therapy (PDT), heat-shock protein 90 (HSP90) down-regulation and chemotherapy (CT), and low-temperature PTT. This proof-of-concept study illustrates an efficient, generalized approach to design high-performance covalent organic framework (COF)-based nanoagents that can be easily tailored to combine different therapeutic modalities for improved cancer theranostics at low temperatures.