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

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

J Control Release

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:

Published: February 2023

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) and Al(OH), which has highly similar components to commercial Imject Alum. Peritumoral injection of NanoAlum effectively neutralized the acidic TME while releasing Mg 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.

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Source
http://dx.doi.org/10.1016/j.jconrel.2023.01.043DOI Listing

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