Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
Adv Healthc Mater. 2021 May;10(9):e2002197. doi: 10.1002/adhm.202002197. Epub 2021 Mar 9.
Supramolecular nanomedicines based on self-assembly of D-peptides have been of great interest as potential candidates for cancer therapy. Neuropilin-1 (NRP1) and mouse double minute 2 (MDM2) have been considered as the anticancer targets because of their overexpression in cancers. However, NRP1/MDM2-targeted D-peptide supramolecular nanomedicines remain unreported. Here, a potent anticancer D-peptide supramolecular nanomedicine targeting NRP1 and MDM2, termed as NMTP-5, is identified by using structure-based virtual screening techniques. NMTP-5 exhibits good biostability and strong cellular uptake performance. Moreover, NMTP-5 displays strong anticancer activity to SK-Hep-1 cells in vitro and in vivo, with no apparent host toxicity. This work demonstrates that NMTP-5 can be used as a potential chemotherapeutic agent for the treatment of liver cancer.
基于 D-肽自组装的超分子纳米药物作为癌症治疗的潜在候选药物受到了极大的关注。神经纤毛蛋白-1（NRP1）和鼠双微体 2（MDM2）由于在癌症中过度表达，被认为是抗癌靶点。然而，针对 NRP1/MDM2 的 D-肽超分子纳米药物仍未见报道。本研究采用基于结构的虚拟筛选技术，鉴定出一种有效的针对 NRP1 和 MDM2 的抗癌 D-肽超分子纳米药物，命名为 NMTP-5。NMTP-5 具有良好的生物稳定性和较强的细胞摄取性能。此外，NMTP-5 在体外和体内均表现出很强的抗癌活性，对 SK-Hep-1 细胞有明显的抑制作用，且宿主毒性较小。本研究表明，NMTP-5 可用作治疗肝癌的潜在化疗药物。
