2. Academic Validation
  3. A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model

  • J Nanobiotechnology. 2022 Jan 29;20(1):54. doi: 10.1186/s12951-022-01265-4.
Xiang-Yu Liu # 1,  Mao-Hua Zhu # 1,  Xiao-Yu Wang 1,  Xiao Dong 1,  Hai-Jun Liu 1,  Rui-Yang Li 1,  Shi-Chong Jia 1,  Qin Lu 1,  Mei Zhao 2,  Peng Sun 3,  Hong-Zhuan Chen 4,  Chao Fang 5 6
Affiliations

Affiliations

  • 1 Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
  • 2 Department of Pharmacy, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Shanghai, 201318, China.
  • 3 Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai, 200336, China.
  • 4 Institute of Interdisciplinary Integrative Biomedical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 5 Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China. fangchao32@sjtu.edu.cn.
  • 6 Key Laboratory of Basic Pharmacology of Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563003, China. fangchao32@sjtu.edu.cn.
  • # Contributed equally.
PMID: 35093074 DOI: 10.1186/s12951-022-01265-4
Abstract

Background: Harnessing the immune system to fight Cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in Cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast Cancer Immunotherapy.

Methods: NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated Anticancer effect were investigated.

Results: Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast Cancer cells and orthotopic breast tumor model in mice.

Conclusions: The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in Cancer Immunotherapy.

Keywords

Breast cancer; Fc fragment; Immunotherapy; Innate immune system; Nanoparticles.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P11746
    MMP2 可裂解肽
    MMP
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