NIR-II Fluorescent Activatable Drug Delivery Nanoplatform for Cancer-Targeted Combined Photodynamic and Chemotherapy.

Nanotheranostics with integrated imaging functions can help monitor nanoparticle accumulation in tumors, thus achieving synergism and higher therapeutic accuracy in cancer therapy. However, it remains challenging to monitor the release of therapeutic drugs in real time from a nanoparticulate drug delivery system (nano-DDS) in the body. Herein, we developed a nano-DDS for fluorescence imaging in the second near-infrared window (NIR-II) region, which can be used for monitoring the responsive release of drugs and cancer-targeted combined photodynamic and chemotherapy. There is a linear correlation between the cumulative release of the drug and the NIR-II fluorescence intensity. Moreover, hyaluronidase/glutathione dual-response RGD-SS-DOX/Ce6@HA-IR-1061 (RSSDCHI) exhibited a higher tumor-to-normal-tissue ratio in NIR-II fluorescence imaging and enhanced antitumor efficacy in vivo. This makes it possible to visualize drug release at the cellular level by the nanocomposites and to predict the treatment effect according to the NIR-II fluorescence intensity in the tumor site, serving as a promising nanoplatform for precision nanomedicine.