Huang Dongyu, Yu Qingyu, Yang Kaiyue, Li Xiuqiang, Huang Chenlu, Yang Xinyu, Wu Chaoxiong, Cao Cheng, Zhang Linhua, Zhu Dunwan, Li Junjie
Department of Polymer Science, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
ACS Appl Bio Mater. 2025 Apr 21;8(4):3356-3374. doi: 10.1021/acsabm.5c00120. Epub 2025 Apr 3.
Melanoma is a highly aggressive and metastatic malignancy, where current treatment methods often result in damage to healthy tissues, suboptimal therapeutic outcomes, and immune-related side effects. Microneedles, as a drug delivery system, offer advantages such as localized administration, minimal invasiveness, and high delivery efficiency. In this study, we first synthesized tetradecyl-thiol-grafted PAMAM dendrimers, which significantly enhanced cellular uptake and enabled sustained release of doxorubicin (DOX), improving cumulative drug release efficiency. Based on this, we developed a core-shell structured zwitterionic polymer-based microneedle delivery system. The outer shell, loaded with the photothermal agent indocyanine green (ICG), achieved precise photothermal therapy under near-infrared irradiation, effectively targeting melanoma tissues. The inner core, composed of a zwitterionic polymer matrix, encapsulated DOX-loaded dendrimers, enabling controlled and prolonged drug release through gradual polymer swelling and dendrimer expansion. Experiments show that the microneedle drug delivery system based on PAMAM dendrimer grafted with tetradecyl mercaptan and zwitterionic polymer has excellent anti protein adsorption properties, and it can minimize the cytotoxicity of carrier and improve the efficiency of drug delivery. This system effectively inhibited tumor growth through synergistic photothermal-chemotherapy, reducing systemic toxicity and improving drug bioavailability. This microneedle platform provides a promising strategy for targeted and synergistic melanoma therapy, offering a high-efficiency and low-toxicity treatment alternative.
黑色素瘤是一种极具侵袭性和转移性的恶性肿瘤，目前的治疗方法常常会对健康组织造成损害，治疗效果欠佳，还会产生免疫相关的副作用。微针作为一种药物递送系统，具有局部给药、微创性和高递送效率等优点。在本研究中，我们首先合成了十四烷基硫醇接枝的聚酰胺-胺（PAMAM）树枝状大分子，其显著增强了细胞摄取并实现了阿霉素（DOX）的持续释放，提高了药物累积释放效率。基于此，我们开发了一种核壳结构的基于两性离子聚合物的微针递送系统。外壳负载光热剂吲哚菁绿（ICG），在近红外照射下实现精确的光热治疗，有效靶向黑色素瘤组织。内核由两性离子聚合物基质组成，包裹着负载DOX的树枝状大分子，通过聚合物逐渐溶胀和树枝状大分子膨胀实现药物的可控和长效释放。实验表明，基于十四烷基硫醇接枝的PAMAM树枝状大分子和两性离子聚合物的微针药物递送系统具有优异的抗蛋白吸附性能，可将载体的细胞毒性降至最低并提高药物递送效率。该系统通过光热-化疗协同作用有效抑制肿瘤生长，降低全身毒性并提高药物生物利用度。这种微针平台为靶向和协同治疗黑色素瘤提供了一种有前景的策略，提供了一种高效低毒的治疗选择。
