Injectable polypeptide-polysaccharide depot for preventing postoperative tumor recurrence by concurrent in situ chemotherapy and brachytherapy

作者：Jiaming Fan, Xiaoyao Cai, Han Gui, Mei Lin, Wei Xu, Dianyu Wang, Youtian Zhang, Chen Gao, Lijun Yang, Cuihong Yang, Jinjian Liu, Yong Guan, Jianfeng Liu · 发表于：Materials Today Bio · 年份：2024 · DOI：10.1016/j.mtbio.2024.101219 · 被引用次数：4 · 研究领域：Nanoparticle-Based Drug Delivery、Nanoplatforms for cancer theranostics、Cancer Research and Treatments

Chemotherapy and radiotherapy in combination with sequence regimens are recognized as the current major strategy for suppressing postoperative tumor recurrence. However, systemic side effects and poor in-field cooperation of the two therapies seriously impair the therapeutic efficacy of patients. The combination of brachytherapy and chemotherapy through innovative biomaterials has proven to be an important strategy to achieve synergistic effects of radiotherapy and chemotherapy in-time and in-field. However, for postoperative chemoradiotherapy, as far as we know, there are few relevant reports. Herein, an injectable pH-responsive polypeptide-polysaccharide depot for concurrent in situ chemotherapy and brachytherapy was developed by encapsulating vincristine into iodine-125 radionuclide labeled hydrogel. This depot hydrogel was prepared by dynamic covalent bonds of Schiff base between aldehydeated hyaluronic acid and polyethylene glycol-polytyrosine. Therefore, this hydrogel enables smart response to tumor acidic microenvironment, rapid release of the encapsulated vincristine and an enhanced uptake effect by tumor cells, which significantly reduces IC 50 of vincristine for the anaplasia Wilms' tumor cells in vitro . This depot hydrogel shows excellent stability and biocompatibility, and maintains for 14 days after in situ injection in a postoperative model of anaplasia Wilms' tumor. After injection at the cavity of tumor excision, responsively-released vincristine and the radi...