journal article·2025-08-12

Chiral Artificial Antigen-Presenting Cells Enhancing Tumor Immunotherapy: Evasion of Macrophage Uptake through Inhibition of Serum Protein Corona Formation

Chao Xing, Xiaoqiu Dou, Laiben Gao, Peng Xu, Yinbo Peng, Kaikai Yang, Yong Fang, Kai Hou, Shegan Gao, Chuanliang Feng

ACS Nano· Volume 19· Issue 31
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Abstract

Biomimetic artificial antigen-presenting cells (aAPCs) have emerged as a promising platform for the immune system activation and modulation. However, abundant serum proteins in the living body prefer to adsorb on the aAPC surface to form a protein corona, leading to rapid clearance of aAPCs by mononuclear phagocytes, causing inefficient tumor immunotherapy by aAPCs. To achieve long-lasting antitumor immunity, chiral aAPCs with left-handed (aAPCs-L) or right-handed (aAPCs-D) helices are constructed via coassembly, chiral induction, chiral memory, and a click reaction. aAPCs-L can efficiently prevent the formation of a protein corona since the left-handed helix of aAPCs-L and the right-handed helix of serum proteins are structurally mismatched. Compared with aAPCs-D and achiral aAPCs (aAPCs-R), aAPCs-L can extend the blood circulation half-life from 4.15–4.72 h to more than 24 h via evading macrophage uptake and clearance, performing sustained activation of antitumor immune response. In vivo treatment with aAPCs-L results in invisible residual melanoma on day 25 (but 947.3 ± 122.8 mm 2 residual melanoma for aAPCs-R and 656.1 ± 135.0 mm 2 residual melanoma for aAPCs-D). This study demonstrates that incorporating the chiral structure into the design of aAPCs improves pharmacokinetics and enhances the efficacy of tumor immunotherapy, which provides useful insights into the development of advanced biomedical materials for cancer treatment.
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Research context

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · HIV Research and Treatment

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Burns and Plastic Surgery & Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital School of Medicine, Shanghai Ninth People’s Hospital and Institute of Traumatic Medicine

Shanghai Jiao Tong University School of Medicine

State Key Lab of Metal Matrix Composites, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Materials Science and Engineering

Shanghai Jiao Tong University

State Key Laboratory of Advanced Fiber Materials, College of Materials Science and Engineering, Donghua University, 2999 North Renmin Road, Shanghai 201620, China

Henan Key Laboratory of Microbiome and Esophageal Cancer, Prevention and Treatment, Henan Key Laboratory of Cancer, Epigenetics, Cancer Hospital

The First Affiliated Hospital of Henan University of Science and Technology

Funding

Biomaterials and Regenerative Medicine Institute Cooperative Research Project, Shanghai Jiaotong University School of Medicine · National Nature Science Foundation of China NSFC · Chinese Postdoctoral Science Foundation · Postdoctoral Fellowship Program of CPSF under Grant Number · The authors gratefully acknowledge the financial supportfrom National Key Research and Development Program

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