Hypoxia-responsive covalent organic framework by single NIR laser-triggered for multimodal synergistic therapy of triple-negative breast cancer

In recent years, laser-mediated photodynamic therapy and photothermal therapy have attracted widespread attention due to their minimally invasive, easy to operate characteristics and high specificity. However, the traditional photodynamic or photothermal therapy exist several shortcomings such as the hypoxic microenvi-ronment, intracellular heat shock proteins or complex operation. In this study, covalent organic framework (COF) was used as the drug carrier to equip with the photosensitizer indocyanine green (ICG) and the hypoxia-activating prodrug AQ4N. The hyaluronic acid (HA) was modified on the surface of COF to obtain the HA-COF@ICG/AQ4N drug delivery system. HA-modified COF delivery systems can target tumor cells through recognize CD44 which is overexpressed in the surface of tumor cells membrane. Under the irradiation of single NIR laser, ICG that can excite the nanoplatform simultaneously produces a combined effect of photodynamic and photothermal. At the same time, photodynamic therapy through depleting intracellular oxygen exacerbates the hypoxic state of the tumor microenvironment, which in turn enhances AQ4N reduced to chemotherapeutic drug AQ4, producing a synergistic cascade antitumor effect. The results of our study by tumor cell and tumor spheroids indicated that the hypoxia-activated multi-functional nanoplatform could effectively inhibit the growth and metastasis of triple-negative breast cancer.

Automated summary

In recent years, laser-mediated photodynamic therapy and photothermal therapy have received significant attention due to their minimally invasive characteristics and high specificity. However, traditional photodynamic or photothermal therapy has certain limitations such as the hypoxic microenvironment and complex operation. This study developed a drug delivery system using covalent organic framework (COF) as a carrier for the photosensitizer indocyanine green (ICG) and the hypoxia-activating prodrug AQ4N, with hyaluronic acid (HA) modified on the surface of COF. The HA-COF@ICG/AQ4N system can target tumor cells through recognizing CD44, which is overexpressed in the surface of tumor cells membrane. Under the irradiation of a single NIR laser, the nanoplatform simultaneously produces a combined effect of photodynamic and photothermal, enhancing the antitumor effect.