Wu Tiantian, Shi Yanqiang, Yang Tao, Zhao Pengxuan, Yang Zhu, Yang Bin
Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University Guangzhou 510091 China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University Haikou 571199 China.
RSC Adv. 2024 Mar 21;14(14):9602-9608. doi: 10.1039/d3ra08146j. eCollection 2024 Mar 20.
Dolastatin derivatives possess excellent anticancer activity and have been translated into clinical trials for cancer therapy. Drug delivery systems enable dolastatin derivatives to break the limitation of instability during blood circulation and ineffective cell internalization in the application. Nevertheless, their potential has not been thoroughly established because of the limited loading efficacy and complicated chemical modification. Herein, we rationally propose a rolling circle amplification-based polymer-DNA assembled nanoflower for targeted and efficient delivery of dolastatin-derived drugs to achieve efficient anticancer therapy. The polymer-DNA assembled nanoflower with targeted aptamer conjugate is widely applicable for loading dolastatin-derived drugs with high encapsulation efficiency. The developed monomethyl auristatin E (MMAE) loaded PN@M exhibited increased cellular uptake and enhanced inhibitory effect, especially in multidrug-resistant tumor cells. The results of anticancer effects indicate that nanoflower as a dolastatin derivatives delivery system holds considerable potential for the treatment of malignant cancer.
多拉司他汀衍生物具有出色的抗癌活性，已进入癌症治疗的临床试验阶段。药物递送系统使多拉司他汀衍生物能够突破其在血液循环中不稳定以及在应用过程中细胞内化效率低下的限制。然而，由于其负载效率有限以及化学修饰复杂，它们的潜力尚未得到充分发挥。在此，我们合理地提出了一种基于滚环扩增的聚合物 - DNA 组装纳米花，用于将多拉司他汀衍生药物靶向且高效地递送，以实现有效的抗癌治疗。带有靶向适配体共轭物的聚合物 - DNA 组装纳米花广泛适用于以高封装效率负载多拉司他汀衍生药物。所开发的负载单甲基澳瑞他汀 E（MMAE）的 PN@M 表现出细胞摄取增加和抑制作用增强，特别是在多药耐药肿瘤细胞中。抗癌效果结果表明，纳米花作为多拉司他汀衍生物递送系统在治疗恶性癌症方面具有巨大潜力。
