Feedback-Elevated Antitumor Amplifier of Self-Delivery Nanomedicine by Suppressing Photodynamic Therapy-Caused Inflammation

Inflammation activation is accompanied by tumor growth,migration,and differentiation. Photodynamic therapy (PDT) can trigger an inflammatoryresponse to cause negative feedback of tumor inhibition. In this paper,a feedback-elevated antitumor amplifier is developed by constructingself-delivery nanomedicine for PDT and cascade anti-inflammation therapy.Based on the photosensitizer chlorin e6 (Ce6) and COX-2 inhibitorindomethacin (Indo), the nanomedicine is prepared via molecular self-assemblytechnology without additional drug carriers. It is exciting that theoptimized nanomedicine (designated as CeIndo) possesses favorablestability and dispersibility in the aqueous phase. Moreover, the drugdelivery efficiency of CeIndo is significantly improved, which couldbe effectively accumulated at the tumor site and internalized by tumorcells. Importantly, CeIndo not only exhibits a robust PDT efficacyon tumor cells but also drastically decreases the PDT-induced inflammatoryresponse in vivo, resulting in feedback-elevated tumor inhibition.By virtue of the synergistic effect of PDT and cascade inflammationsuppression, CeIndo tremendously reduces tumor growth and leads toa low side effect. This study presents a paradigm for the developmentof codelivery nanomedicine for enhanced tumor therapy through inflammationsuppression.