Engineered NanoAlum from aluminum turns cold tumor hot for potentiating cancer metalloimmunotherapy

Yingbo Jia; Jing Hu; Chaojie Zhu; Zijing Li; Xinyu Yang; Ruitian Liu; Linghui Zeng; Lingxiao Zhang

doi:10.1016/j.jconrel.2023.01.043

Engineered NanoAlum from aluminum turns cold tumor hot for potentiating cancer metalloimmunotherapy

J Control Release. 2023 Feb:354:770-783. doi: 10.1016/j.jconrel.2023.01.043. Epub 2023 Jan 27.

Authors

Yingbo Jia¹, Jing Hu², Chaojie Zhu³, Zijing Li³, Xinyu Yang³, Ruitian Liu⁴, Linghui Zeng⁵, Lingxiao Zhang⁶

Affiliations

¹ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
² Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 211200, China.
³ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China.
⁴ State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
⁵ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China. Electronic address: [email protected].
⁶ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, China. Electronic address: [email protected].

PMID: 36702259
DOI: 10.1016/j.jconrel.2023.01.043

Abstract

The poor cancer immunotherapy outcome has been closely related to immunosuppressive tumor microenvironment (TME), which usually inactivates the antitumor immune cells and leads to immune tolerance. Metalloimmunotherapy by supplementing nutritional metal ions into TME has emerged as a potential strategy to activate the tumor-resident immune cells. Herein, we engineered a magnesium-contained nano-aluminum adjuvant (NanoAlum) through hydrolyzing a mixture of Mg(OH)₂ and Al(OH)₃, which has highly similar components to commercial Imject Alum. Peritumoral injection of NanoAlum effectively neutralized the acidic TME while releasing Mg²⁺ to activate the tumor-resident T cells. Meanwhile, NanoAlum also blocked the autophagy pathway in tumor cells and subsequently induced cell apoptosis. The in vivo studies showed that merely peritumoral injection of NanoAlum successfully inhibited the growth of solid tumors in mice. On this basis, NanoAlum combined with chemical drug methotrexate or immunomodulatory adjuvant CpG further induced potent antigen-specific antitumor immunity. Overall, our study first provides a rational design for engineering tumor-targeted nanomodulator from clinical adjuvants to achieve effective cancer metalloimmunotherapy against solid tumors.

Keywords: Aluminum adjuvants; In situ immunotherapy; Layered double hydroxide; Metalloimmunotherapy; Tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Adjuvants, Pharmaceutic / pharmacology
Aluminum* / pharmacology
Aluminum* / therapeutic use
Animals
Immunotherapy
Mice
Neoplasms* / drug therapy
T-Lymphocytes
Tumor Microenvironment

Substances

Aluminum
Adjuvants, Immunologic
Adjuvants, Pharmaceutic