Synergistic Photothermal Therapy and Chemotherapy Enabled by Tumor Microenvironment-Responsive Targeted SWCNT Delivery

Abstract

As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH2) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment.