J. F. Tan, Jiqian Zhang, Minglong Chen, Jie Cen, Wenli Wang, Chunyu You, Xianglong Hu, Jinming Hu, Shiyong Liu
Over 75% of patients with advanced-stage tumors experience severe cancer-associated pain, yet current opioid-based therapies are limited by dose-dependent toxicity, adverse side effects, and poor delivery control. Here, we present a light-responsive meltable polycarbonate polymersome (MPP) micro-analgesia pump, self-assembled from Nile blue-labeled polycarbonate block copolymers encapsulating tetrodotoxin (TTX), a non-opioid analgesic. The MPPs effectively suppress spontaneous TTX leakage under dark conditions, thereby minimizing off-target toxicity, while enabling on-demand release upon red light irradiation. This release is driven by localized photothermal heating of aggregated Nile blue moieties, which induces melting of the polycarbonate bilayer membrane. In addition, the photoresponsive system integrates photothermal and photodynamic effects to inhibit tumor growth while simultaneously alleviating tumor-induced pain. Overall, this strategy provides a promising non-opioid approach for concurrent management of cancer pain and tumor progression.