ABSTRACT Multimodal tumor therapies suffer from poor spatial co‐localization, asynchronous activation, and weak cross‐modal reinforcement, leading to limited therapeutic efficiency. Here, we report a photoelectric therapy needle (PTN) system that achieves in situ synchronous electrothermal‐photodynamic therapy (synchronous ETT‐PDT) and amplifies chemotherapeutic efficacy through hierarchical cross‐modal and cross‐component reinforcement. The PTN integrates optical fibers and heating wires within a single hollow needle, enabling precise, spatiotemporally synchronized activation under ultralow energy (0.2 V, 0.1 W cm −2 ). We further designed hyaluronic acid‐modified MOF@infinite coordination polymer nanocomposites (HA‐MOF@ICP NCPs) co‐loaded with ICG, SN38, and AQ4N for sequential release. This structure allows PDT‐induced hypoxia to activate AQ4N, while ETT enhances SN38 cytotoxicity, establishing a bidirectional ETT↔PDT reinforcement and multi‐level drug synergy. In vivo, PTN‐NCPs achieved complete eradication of large tumors (≈300 mm 3 ) within 21 days using one‐tenth conventional PDT energy and minimal drug doses (1/2.5 AQ4N, 1/12.5 SN38), with no recurrence over 60 days. Four parameters of toxicity, energy, dosage and therapeutic effect were selected and normalized to assess the cost‐effective degree of our mutually reinforcing strategy. Compared with the results of prior trimodal strategies, our mutually reinforcing strategy had the largest cost‐effective degree value (1.6–10.9 times high), achieving high cost‐effective tumor comprehensive therapeutic outcomes.
Wang et al. (Wed,) studied this question.