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 inflammatory response to cause negative feedback of tumor inhibition. In this paper, a feedback-elevated antitumor amplifier is developed by constructing self-delivery nanomedicine for PDT and cascade anti-inflammation therapy. Based on the photosensitizer chlorin e6 (Ce6) and COX-2 inhibitor indomethacin (Indo), the nanomedicine is prepared via molecular self-assembly technology without additional drug carriers. It is exciting that the optimized nanomedicine (designated as CeIndo) possesses favorable stability and dispersibility in the aqueous phase. Moreover, the drug delivery efficiency of CeIndo is significantly improved, which could be effectively accumulated at the tumor site and internalized by tumor cells. Importantly, CeIndo not only exhibits a robust PDT efficacy on tumor cells but also drastically decreases the PDT-induced inflammatory response in vivo, resulting in feedback-elevated tumor inhibition. By virtue of the synergistic effect of PDT and cascade inflammation suppression, CeIndo tremendously reduces tumor growth and leads to a low side effect. This study presents a paradigm for the development of codelivery nanomedicine for enhanced tumor therapy through inflammation suppression.