Ding Chensheng, Liu Nian, Chen Zhengwei, Wu Zhuolin, Mao Chun, Wu Ziyu, Xie Yuan, Wan Mimi
National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Department of Vascular Surgery, Cardiovascular Medical Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Int J Pharm. 2025 Aug 20;681:125820. doi: 10.1016/j.ijpharm.2025.125820. Epub 2025 Jun 6.
Due to the particularity of melanoma location, traditional drug delivery methods face difficulties in penetrating skin tissue and specifically clearing melanoma cells. Here, we designed a hyaluronic acid microneedle drug delivery system loaded with nanomotors which can effectively penetrate the skin tissue and deliver the therapeutic components to melanoma and specifically remove melanoma cells. The loaded nanomotors were prepared by radical polymerization of methacryloyl modified L-arginine (MA) and L-tyrosine (MTyr), named as MA/MTyr nanomotor. The microneedle drug delivery system can use the rigid structure of microneedles to break through the skin barrier and deliver nanomotors to deep tissues. The MA endowed them with the ability to sensitively sense the highly expressed inducible nitric oxide synthase in the tumor microenvironment, so as to realize the effective targeting of melanoma in skin tissue and uptake by tumor cells. Subsequently, the MTyr can produce quinone-enriched intermediates that can induce cell death under the catalysis of tyrosinase that was specifically highly expressed in melanoma cells, and self-assembled to form micron scale fibers through intermolecular hydrogen bonding interactions, thereby inducing melanoma cells to swell. This process synergistically promoted melanoma cell death without occurring in normal cells. The experimental results of cell and animal models confirmed the good therapeutic effect of the nanomotor loaded microneedles, which provided a new therapeutic concept and strategy for the development of therapeutic methods specifically for melanoma.
由于黑色素瘤位置的特殊性，传统的药物递送方法在穿透皮肤组织和特异性清除黑色素瘤细胞方面面临困难。在此，我们设计了一种负载纳米马达的透明质酸微针药物递送系统，其能够有效穿透皮肤组织并将治疗成分递送至黑色素瘤，特异性清除黑色素瘤细胞。负载的纳米马达通过甲基丙烯酰基修饰的L-精氨酸（MA）和L-酪氨酸（MTyr）的自由基聚合制备，命名为MA/MTyr纳米马达。微针药物递送系统可利用微针的刚性结构突破皮肤屏障，将纳米马达递送至深层组织。MA赋予它们灵敏感知肿瘤微环境中高表达的诱导型一氧化氮合酶的能力，从而实现对皮肤组织中黑色素瘤的有效靶向及被肿瘤细胞摄取。随后，MTyr可产生富含醌的中间体，其在黑色素瘤细胞中特异性高表达的酪氨酸酶催化下可诱导细胞死亡，并通过分子间氢键相互作用自组装形成微米级纤维，从而诱导黑色素瘤细胞肿胀。这一过程协同促进黑色素瘤细胞死亡，而正常细胞中不会发生。细胞和动物模型的实验结果证实了负载纳米马达的微针具有良好的治疗效果，为开发专门针对黑色素瘤的治疗方法提供了新的治疗理念和策略。
