NIR-II-triggered hollow mesoporous polydopamine nano-depot for integrated photothermal therapy and sustained cancer pain relief.

The short duration of action of ropivacaine (ROP) substantially limits its efficacy in cancer pain management. In this study, we developed a hollow mesoporous polydopamine nano-depot (HMP) for efficient ROP loading and externally controlled release. The resulting HMPR platform achieved a high ROP loading capacity of 42.82%. Upon irradiation with deep-tissue-penetrating NIR-II light at 1064 nm, HMPR enabled rapid on-demand ROP release followed by sustained diffusion. In a murine model of sciatic nerve tumor-induced cancer pain, a single HMPR injection combined with brief NIR-II irradiation prolonged the analgesic duration to more than 8 h, exceeding twice that achieved with free ROP. Meanwhile, HMPR-mediated photothermal therapy effectively ablated subcutaneous tumors. Transcriptomic analysis of dorsal root ganglia further indicated that the prolonged analgesic effect was associated with metabolic and immune rebalancing, characterized by enhanced mitochondrial bioenergetic activity and attenuated neuroinflammatory signaling. Together with its favorable biocompatibility, this all-in-one platform offers a promising non-opioid strategy for combined cancer therapy and sustained pain management.