Novel biomimetic mesoporous silica nanoparticle system possessing targetability and immune synergy facilitates effective solid tumor immuno-chemotherapy

Haoran Zhu; Yang Liu; Xinfeng Yi; Chuyun Zhu; Yuanyue Fu; Zerong Huang; Kairui Zhu; Wencai Zhang; Huige Hou; Chenghong Sun; Cheng Zhong; Wei Liu; Zhizhong Li; Baocheng Wang; Jin Wo

doi:10.1016/j.bioadv.2022.213229

Novel biomimetic mesoporous silica nanoparticle system possessing targetability and immune synergy facilitates effective solid tumor immuno-chemotherapy

Biomater Adv. 2023 Jan:144:213229. doi: 10.1016/j.bioadv.2022.213229. Epub 2022 Dec 5.

Authors

Haoran Zhu¹, Yang Liu¹, Xinfeng Yi², Chuyun Zhu³, Yuanyue Fu¹, Zerong Huang¹, Kairui Zhu¹, Wencai Zhang¹, Huige Hou¹, Chenghong Sun⁴, Cheng Zhong⁵, Wei Liu⁶, Zhizhong Li⁷, Baocheng Wang⁸, Jin Wo⁹

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital and The Fifth Affiliated Hospital, Jinan University, Guangzhou, China.
² Department of Neurosurgery, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, China.
³ The Biomedical Translational Research Institute, Jinan University Faculty of Medical Science, Jinan University, Guangzhou, China.
⁴ State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi, China.
⁵ The Affiliated Hospital (Jiangmen Traditional Chinese Medicine Hospital), Jinan University, Guangzhou, China.
⁶ School of Food Science and Engineering, South China University of Technology, Guangzhou, China. Electronic address: lw2008aoyun@126.com.
⁷ Department of Orthopedics, The First Affiliated Hospital and The Fifth Affiliated Hospital, Jinan University, Guangzhou, China. Electronic address: lizhizhongjd@163.com.
⁸ Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China. Electronic address: wbczhz@163.com.
⁹ Department of Orthopedics, The First Affiliated Hospital and The Fifth Affiliated Hospital, Jinan University, Guangzhou, China; Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China. Electronic address: wj0701@jnu.edu.cn.

PMID: 36502749
DOI: 10.1016/j.bioadv.2022.213229

Abstract

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8⁺ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.

Keywords: Breast tumor; CD80; Immunoregulation; Immunotherapy; Mesoporous silica; Tumor targetability.

MeSH terms

Biomimetics
Humans
Immunotherapy
Nanoparticles*
Neoplasms*
Porosity
Silicon Dioxide

Substances

Silicon Dioxide