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Vol. 13 (2021)

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

https://doi.org/10.1007/s40820-021-00647-x
Liping Huang
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
Yiyi Zhang
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
Yanan Li
State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, and Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China
Fanling Meng
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
Hongyu Li
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
Huimin Zhang
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China
Jiasheng Tu
State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, and Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China
Chunmeng Sun
State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, and Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China
Liang Luo
College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China

Corresponding Author: Liang Luo

liangluo@hust.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 141

Abstract

The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery 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-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.


Highlights:


1 A novel injectable double-layer-gel matrix is developed.
2 The hierarchically structured dual lipid gel matrix enables time-programmed drug delivery.
3 Applying a modest dose of sorafenib in advance can reeducate tumor-associated macrophages and potentiate anti-CD47 treatment.

Keywords

Hierarchical hydrogel Sorafenib Postoperative immunosuppression reversal Tumor-associated macrophages Anti-CD47 antibody
Huang, Liping, Yiyi Zhang, Yanan Li, Fanling Meng, Hongyu Li, Huimin Zhang, Jiasheng Tu, Chunmeng Sun, and Liang Luo. 2021. “Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer”. Nano-Micro Letters 13 (June):141. https://doi.org/10.1007/s40820-021-00647-x.
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