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微创注射凝胶用于肝癌和胃癌的局部免疫治疗。

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China.

出版信息

Adv Sci (Weinh). 2024 Oct;11(38):e2405935. doi: 10.1002/advs.202405935. Epub 2024 Aug 8.

Abstract

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4-arm polyethylene glycol hydroxylamine (4-arm PEG-ONH) through oxime bonds, which can be injected through a clinic-used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.

摘要

局部免疫疗法代表了一种很有前途的解决方案,可以通过消除残留肿瘤细胞并引发肿瘤特异性免疫反应来预防肿瘤切除术后的复发和转移。微创外科已成为全球主流的手术方法,因为它具有美学和快速术后恢复的优势。不幸的是,目前报道的局部免疫治疗策略大多设计用于剖腹手术后,这与微创治疗的当前手术理念背道而驰,不适合临床转化。针对这个问题,本文报道了一种微创可注射凝胶(MIGel),用于治疗胃癌和肝癌术后治疗。MIGel 通过肟键交联氧化葡聚糖(ODEX)和 4 臂聚乙二醇羟胺(4 臂 PEG-ONH)形成,可以通过临床使用的微创引流管注射,并紧密附着在组织上。负载的奥沙利铂(OxP)和瑞喹莫德(R848)可以在两周内持续释放,并在原位小鼠胃癌和肝癌模型中产生超过 75%的治愈率。总之,提出了微创局部免疫治疗的概念,并设计了 MIGel 通过微创外科进行局部腹腔内癌症免疫治疗,具有良好的临床转化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9809/11481255/dfef1362d6b6/ADVS-11-2405935-g003.jpg

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