Pan Yanzhu, Fan Zhongxiong, Yu Shaoqi, Xia Lijie, Li Jinyao
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830017, China.
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830017, China.
Colloids Surf B Biointerfaces. 2025 Mar;247:114411. doi: 10.1016/j.colsurfb.2024.114411. Epub 2024 Nov 26.
Although antimicrobial peptides (AMPs) as a promising natural drugs can efficiently inhibit cervical cancer, poor bioavailability, low tumor selectivity, and non-selective toxicity still hinder its further application in vivo. In order to effectively address these challenges, we have developed a reactive oxygen species (ROS)-responsive targeting nanoprodrug designed for selective therapy of cervical cancer. Such nanoprodrugs (CEC-OxbCD) are fabricated by the supramolecular self-assembly of the modified β-cyclodextrin (β-CD) and AMPs. Antimicrobial peptide, CecropinXJ (CEC), is a cationic antibacterial peptide isolated from 3rd instar larvae of Bombyx mori from Xinjiang, China. OxbCD is an oxidation-responsive β-cyclodextrin material. CEC-OxbCD were synthesized using the nanoprecipitation/self-assembly method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behaviour of CEC-OxbCD were characterised. In vitro and in vivo anti-cancer activities were also evaluated. Nanoprodrugs can be effectively disassembled under stimuli of the tumor- endogenous ROS, resulting in a rapid and on-demand release of antimicrobial peptides (AMPs) with a release rate of 90 %. Furthermore, both in vitro and in vivo experimental results demonstrate that our nanoprodrugs exhibit remarkable therapeutic efficacy against cervical cancer. This work not only provides an effective and promising therapeutic strategy for cervical cancer, but also explores a novel application for AMPs.
尽管抗菌肽作为一种有前景的天然药物能够有效抑制宫颈癌，但较差的生物利用度、低肿瘤选择性和非选择性毒性仍然阻碍了其在体内的进一步应用。为了有效应对这些挑战，我们开发了一种用于宫颈癌选择性治疗的活性氧（ROS）响应靶向纳米前药。这种纳米前药（CEC-OxbCD）是通过修饰的β-环糊精（β-CD）与抗菌肽的超分子自组装制备而成。抗菌肽天蚕素XJ（CEC）是从中国新疆家蚕三龄幼虫中分离得到的一种阳离子抗菌肽。OxbCD是一种氧化响应性β-环糊精材料。CEC-OxbCD采用纳米沉淀/自组装方法合成。随后，对CEC-OxbCD的粒径分布、形态、载药效率和释放行为进行了表征。还评估了其体外和体内抗癌活性。纳米前药在肿瘤内源性ROS刺激下可有效分解，从而快速按需释放抗菌肽（AMPs）且释放率达90%。此外体外和体内实验结果均表明，我们开发的纳米前药对宫颈癌具有显著的治疗效果。这项工作不仅为宫颈癌提供了一种有效且有前景的治疗策略，还探索了抗菌肽的一种新应用。
