Supramolecular engineering of cell membrane vesicles for cancer immunotherapy

Shaolong Qi; Haiyan Zhang; Xueyan Zhang; Xinyang Yu; Yajun Wang; Qian-Fang Meng; Kai Yang; Bing Bai; Rui Tian; Shoujun Zhu; Lang Rao; Feihe Huang; Guocan Yu

doi:10.1016/j.scib.2022.08.030

Supramolecular engineering of cell membrane vesicles for cancer immunotherapy

Sci Bull (Beijing). 2022 Sep 30;67(18):1898-1909. doi: 10.1016/j.scib.2022.08.030. Epub 2022 Aug 24.

Authors

Shaolong Qi¹, Haiyan Zhang², Xueyan Zhang¹, Xinyang Yu¹, Yajun Wang², Qian-Fang Meng³, Kai Yang⁴, Bing Bai¹, Rui Tian⁵, Shoujun Zhu⁶, Lang Rao⁷, Feihe Huang⁴, Guocan Yu⁸

Affiliations

¹ Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
² State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
³ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China.
⁴ State Key Laboratory of Chemical Engineering, Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou 310027, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China.
⁵ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine School of Public Health, Xiamen University, Xiamen 361102, China.
⁶ State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China. Electronic address: sjzhu@jlu.edu.cn.
⁷ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: lrao@szbl.ac.cn.
⁸ Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China. Electronic address: guocanyu@mail.tsinghua.edu.cn.

PMID: 36546304
DOI: 10.1016/j.scib.2022.08.030

Abstract

The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles, promoting scientists to search for novel nanocarriers. Although cell membrane-based delivery systems have attracted extensive attention, further functionalizations are urgently desired to augment their theranostic functions. We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host-guest molecular recognitions to fix the defects arising from chemical and genetic modifications. In this study, the supramolecular cell membrane vesicles (SCMVs) specifically accumulate in tumors, benefiting from tumor-homing capability and the enhanced permeability and retention effect. SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy. Driven by host-guest inclusion complexation, SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype, synergizing with immune checkpoint blockade therapy. This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell-originated nanomaterials for precise cancer therapy.

Keywords: Cancer theranostics; Host–guest systems; Immunotherapy; Nanomedicine; Supramolecular chemistry.

MeSH terms

Cell Membrane
Cyclodextrins*
Humans
Immunotherapy
Nanostructures*
Neoplasms* / therapy

Substances

Cyclodextrins