Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

纳米颗粒 (NPs) 已在癌症治疗中显示出潜力，但仍无法获得令人满意的单一给药。为了解决这个问题，开发了溶解微针（DMNs）以结合化学疗法和光热疗法（PTT）局部递送功能化纳米颗粒。α-生育酚聚乙二醇琥珀酸酯 (TPGS)/透明质酸 (HA) 双功能化 PLGA NPs (HD10 NPs) 被制造为共同负载紫杉醇和吲哚菁绿。由于 HA 和 TPGS 分别具有活性和线粒体靶向作用，HD10 NPs 显着增强了低剂量紫杉醇的细胞毒性。PTT可以通过促进细胞凋亡进入晚期，高度激活caspase 3酶，并显着降低survivin和MMP-9蛋白的表达，进一步使肿瘤细胞对化疗敏感。此外，对4T1荷瘤小鼠进行了通过不同给药途径递送的HD10 NPs的抗肿瘤作用。单次给药后，与 DMNs 一起递送的 HD10 NPs 在单独给予化疗时显示出最好的抗肿瘤效果。正如预期的那样，联合治疗后抗肿瘤效果显着增强，DMNs和瘤内注射小鼠肿瘤完全消融。此外，由于中度高温，DMN 显示出更好的安全性。因此，DMNs 结合化学光热疗法为浅表肿瘤提供了一种可行的治疗选择。