Carry-On Nitric-Oxide Luggage for Enhanced Chemotherapeutic Efficacy.

In this work, we proposed a carry-on nitric-oxide (NO) luggage strategy for enhanced chemotherapeutic efficacy. A stimuli-responsive NO-releasing polypeptide was prepared as the building block to assemble into a micelle as a chemodrug-carrier. The micelle was anchored with cRGD peptide with the aim of targeting to tumors' neoangiogenesis. In situ generation of NO at the tumor site can promote the neovascularization to recruit more chemotherapeutics. Besides, the introduced exogenous NO can directly induce apoptosis, synergistically with the chemotherapeutics. A specific near-infrared-region (NIR) NO-probe was also developed to be coloaded to the micelle to report the in situ NO-release. In vitro and in vivo experiments were performed to demonstrate the targeting capability, increased accumulation, real-time NO-release reporting phenomenon, improved antitumor efficacy, and favorable biosafety. Embedding NO into drug cargo as carry-on luggage for enhanced chemotherapeutic efficacy, hopefully, can cast new lights and build a basic principle in the future clinical translation of nanomedicines.