School of Pharmaceutical Sciences (Shenzhen) , Sun Yat-sen University , Guangzhou 510275 , China.
ACS Appl Mater Interfaces. 2019 Jul 10;11(27):23948-23956. doi: 10.1021/acsami.9b09031. Epub 2019 Jun 25.
In this work, we prepared a novel cancer chemotherapeutic nanocarrier through the self-assembly of a mussel-derived, cancer-targeting peptide with a pH-sensitive conjugation of antitumor drugs. The biomimetic peptide was designed with a fluorescent molecule fluorescein isothiocyanate for imaging, a RGD sequence for cancer-targeting and tetravalent catechol groups for dynamic conjugation of the antitumor drug bortezomib via pH-cleavable boronic acid-catechol esters. Our study demonstrated that the peptide-based prodrug nanocarrier dramatically the enhanced specific cellular uptake and cytotoxicity toward human breast cancer cells in vitro in comparison with free drug and nontargeting control nanoparticles. Likewise, the prodrug nanocarrier showed improved therapeutic efficacy and low systematic toxicity in vivo. Considering highly biomimetic nature of the peptide-based nanocarriers, rapid drug release from the dynamically conjugated prodrugs, and convenience of introducing cancer-targeting activity onto this nanosystem, we believe our work would provide new ideas for the development of intelligent and biocompatible drug delivery systems to improve the chemotherapy efficacy in clinic. Furthermore, the pH-sensitive drug conjugation mechanism on peptide-based nanocarriers would provide a hint for the exploitation of dynamic prodrug strategies and the development of highly biocompatible nanocarriers using biogenic materials, e.g., the proteinogenic nanomaterials decorated with drugs through dynamic covalent chemistry.
在这项工作中，我们通过自组装贻贝类癌症靶向肽与 pH 敏感的抗肿瘤药物缀合物制备了一种新型癌症化疗纳米载体。仿生肽设计有荧光分子异硫氰酸荧光素用于成像，RGD 序列用于癌症靶向，四价儿茶酚基团用于通过 pH 可裂解硼酸-儿茶酚酯动态缀合抗肿瘤药物硼替佐米。我们的研究表明，与游离药物和非靶向对照纳米颗粒相比，基于肽的前药纳米载体显著增强了人乳腺癌细胞的特异性细胞摄取和体外细胞毒性。同样，前药纳米载体在体内表现出更好的治疗效果和低系统毒性。考虑到基于肽的纳米载体的高度仿生性质、从动态缀合前药中快速释放药物以及在纳米系统上引入癌症靶向活性的便利性，我们相信我们的工作将为开发智能和生物相容的药物输送系统以提高临床化疗效果提供新的思路。此外，基于肽的纳米载体上的 pH 敏感药物缀合机制为开发动态前药策略和使用生物源材料（例如通过动态共价化学修饰的药物的蛋白纳米材料）开发高度生物相容的纳米载体提供了线索。
