One-photon red light-triggered disassembly of small-molecule nanoparticles for drug delivery

Background: Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet-triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states. Results: Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo. Conclusions: This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.

Automated summary

Photoresponsive drug delivery using red light to trigger one-photon upconversion-like photolysis for cancer therapy has been successfully demonstrated. The nanoparticles protected the photolysis process from oxygen quenching, resulting in efficient drug release upon red light irradiation. The red light-triggered drug release system showed promising anti-tumor efficacy in both in vitro and in vivo experiments, providing a practical reference for future photoresponsive nanocarrier development.