Han Weiqiang, Yu Lan, Liu Zhuo, Wang Chaofan, Zhang Qi, Li Hongjuan, Xu Yongqian, Liu Fengyu, Sun Shiguo
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, China.
State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian, 116023, PR China.
ChemMedChem. 2025 Jan 2;20(1):e202400537. doi: 10.1002/cmdc.202400537. Epub 2024 Nov 8.
Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models.
黑色素瘤已成为对人类生命和健康的重大威胁。微针介导的经皮给药在黑色素瘤治疗中受到关注，因为它可以绕过首过效应。然而，黑色素瘤的转移倾向给微针介导的局部治疗带来了巨大挑战。开发全身治疗方法，如免疫疗法与经皮给药相结合，对于实现有效的黑色素瘤治疗至关重要。在此，开发了一种聚乙烯醇（PVA）微针介导的多功能经皮给药系统，命名为MN@PDA@1-MT/CUR/DOX@HA（MN@PMCDH），用于黑色素瘤的协同化疗/光热/免疫治疗。PMCDH纳米药物通过微针穿透深层皮肤，在透明质酸（HA）的引导下在肿瘤部位聚集，并响应酸性肿瘤微环境和近红外（NIR）刺激选择性释放药物。释放的姜黄素（CUR）显著增强了光热疗法（PTT）和化疗的疗效，以及通过增加黑色素瘤对聚多巴胺（PDA）介导的光热效应和阿霉素（DOX）的敏感性来改善免疫原性细胞死亡（ICD）的诱导。此外，加入1-甲基色氨酸（1-MT）以逆转肿瘤免疫抑制微环境可进一步增强免疫治疗效果。体外研究表明，MN@PMCDH系统可有效诱导ICD并抑制肿瘤细胞生长。此外，在三维肿瘤模型中也实现了显著的深部肿瘤细胞抑制效果。
