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mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy.

Publication ,  Journal Article
Zhu, Y; Yao, Z-C; Li, S; Ma, J; Wei, C; Yu, D; Stelzel, JL; Ni, BYX; Miao, Y; Van Batavia, K; Lu, X; Lin, J; Dai, Y; Kong, J; Shen, R ...
Published in: bioRxiv
January 29, 2025

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 potent transfection efficiency of LNPs in antigen-presenting cells (APCs), LiNx demonstrates remarkable immune cell recruitment, antigen expression and presentation, and cellular interaction. These attributes collectively create an immunostimulating milieu and yield a potent immune response achievable with a single dose, comparable to the conventional three-dose LNP immunization regimen. Further investigations reveal that the LiNx not only generates heightened Th1 and Th2 responses but also elicits a distinctive Type 17 T helper cell-mediated response pivotal for bolstering antitumour efficacy. Our findings elucidate the mechanism underlying LiNx's role in potentiating antigen-specific immune responses, presenting a new strategy for cancer immunotherapy.

Duke Scholars

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Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

January 29, 2025

Location

United States
 

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Zhu, Y., Yao, Z.-C., Li, S., Ma, J., Wei, C., Yu, D., … Mao, H.-Q. (2025). mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy. BioRxiv. https://doi.org/10.1101/2025.01.27.633179
Zhu, Yining, Zhi-Cheng Yao, Shuyi Li, Jingyao Ma, Christine Wei, Di Yu, Jessica L. Stelzel, et al. “mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy.BioRxiv, January 29, 2025. https://doi.org/10.1101/2025.01.27.633179.
Zhu Y, Yao Z-C, Li S, Ma J, Wei C, Yu D, Stelzel JL, Ni BYX, Miao Y, Van Batavia K, Lu X, Lin J, Dai Y, Kong J, Shen R, Goodier KD, Liu X, Cheng L, Vuong I, Howard GP, Livingston NK, Choy J, Schneck JP, Doloff JC, Reddy SK, Hickey JW, Mao H-Q. mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy. bioRxiv. 2025 Jan 29;

Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

January 29, 2025

Location

United States