Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

• 作者: Liping Huang Yiyi Zhang Yanan Li Fanling Meng Hongyu Li Huimin Zhang Jiasheng Tu Chunmeng Sun Liang Luo
• 来源期刊: 纳微快报（英文版）
• 年，卷（期）: 2021,（9）
• 页码范围: 353-367
• 页数: 15页
• 语种: 英文

摘要

The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients.Program-mable delivery of immunotherapy-involving combinations through a single drug defivery system is highly promising,yet greatly challenging,to reverse postoperative immunosuppression.Here,an injectable hierarchical gel matrix,composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios,was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy.The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles.GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages(TAMs) and promote an immunogenic tumor microenvironment.The inner layer,loaded with anti-CD47 antibody (aCD47),could maintain the gel state for a much longer time,enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect.In vivo studies on 4T1 tumor-beating mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosup-pression and synergistically blocking the CD47-dependent immune escape,thereby boosting the systemic immune responses.