Molecular Sciences and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, P. R. China.
Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
ACS Appl Mater Interfaces. 2021 Mar 3;13(8):9436-9444. doi: 10.1021/acsami.0c18282. Epub 2020 Dec 11.
High levels of heat shock protein 70 (HSP70) in tumors are commonly associated with poor prognosis, enhanced doxorubicin (DOX)-induced cardiotoxicity, and even drug resistance in DOX-related cancer chemotherapy. Several peptides possess remarkable protein inhibition and chemosensitization effects, which are attributed to their specific targeting ability against HSP70. However, the inherent poor cell penetration capacity considerably restricts the biomedical applications of these peptides. We herein describe the design and development of anti-MUC1 aptamer-peptide conjugates (ApPCs) as targeted chemosensitizers to overcome the above-mentioned issues. Moreover, DOX could be loaded on the ApPC to deliver the DOX-enclosed agent ApPC-DOX, which simultaneously acts as a targeted chemosensitizer and anticancer agent for combating drug resistance in breast cancer therapy. This innovative, engineered biocompatible conjugate not only enhances the sensitivity of DOX-resistant cells but also alleviates cardiotoxicity of DOX , highlighting the success of this targeted chemosensitizer strategy.
肿瘤中高水平的热休克蛋白 70（HSP70）通常与预后不良、增强多柔比星（DOX）诱导的心脏毒性，甚至与 DOX 相关的癌症化疗中的耐药性相关。一些肽具有显著的蛋白抑制和化疗增敏作用，这归因于它们对 HSP70 的特异性靶向能力。然而，内在的细胞穿透能力差极大地限制了这些肽的生物医学应用。我们在此描述了抗 MUC1 适体-肽缀合物（ApPC）的设计和开发，作为靶向化疗增敏剂，以克服上述问题。此外，DOX 可以装载在 ApPC 上，以递送 DOX 封闭的药物 ApPC-DOX，它同时作为一种靶向化疗增敏剂和抗癌剂，用于对抗乳腺癌治疗中的耐药性。这种创新的、工程化的生物相容性缀合物不仅增强了 DOX 耐药细胞的敏感性，而且减轻了 DOX 的心脏毒性，突出了这种靶向化疗增敏策略的成功。
