An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy

An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy

Abstract Hydrogel materials have emerged as versatile platforms for various biomedical applications. Notably, the engineered nanofiber-hydrogel composite (NHC) has proven effective in mimicking the soft tissue extracellular matrix, facilitating substantial recruitment of host immune cells and the fo...

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Main Authors: Yining Zhu, Zhi-Cheng Yao, Shuyi Li, Jingyao Ma, Christine Wei, Di Yu, Jessica L. Stelzel, Bobby Y. X. Ni, Yang Miao, Kyra Van Batavia, Xiaoya Lu, Jinghan Lin, Yifan Dai, Jiayuan Kong, Ruochen Shen, Kailei D. Goodier, Xiang Liu, Leonardo Cheng, Ivan Vuong, Gregory P. Howard, Natalie K. Livingston, Joseph Choy, Jonathan P. Schneck, Joshua C. Doloff, Sashank K. Reddy, John W. Hickey, Hai-Quan Mao
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61299-8
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Summary:Abstract Hydrogel materials have emerged as versatile platforms for various biomedical applications. Notably, the engineered nanofiber-hydrogel composite (NHC) has proven effective in mimicking the soft tissue extracellular matrix, facilitating substantial recruitment of host immune cells and the formation of a local immunostimulatory microenvironment. Leveraging this feature, here we report an mRNA lipid nanoparticle (LNP)-incorporated NHC microgel matrix, termed LiNx, by incorporating LNPs loaded with mRNA encoding tumour antigens. Harnessing the high transfection efficiency of LNPs in antigen-presenting cells, LiNx demonstrates substantial levels of immune cell recruitment, antigen expression and presentation, and cellular interaction. These attributes collectively create an immunostimulating microenvironment and yield a potent immune response with a single dose at a level comparable to the conventional three-dose LNP immunization protocol. Further investigation reveals that the LiNx generates not only high levels of Th1 and Th2 responses, but also a distinct Type 17 T helper cell response critical for bolstering antitumour efficacy. Our findings elucidate the mechanism underlying LiNx’s role in potentiating antigen-specific immune responses, presenting a strategy for cancer immunotherapy.
ISSN:2041-1723

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