Calcium Carbonate/Polydopamine Composite Nanoplatform Based on TGF‑β Blockade for Comfortable Cancer Immunotherapy

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO₃/PDA nanoparticles (CaPNM_CUR+Ropi) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNM_CUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-β) and inflammatory factor (IL-6, IL-1β, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-β leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.