Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy

Fuhao Jia; Wenping Huang; Yue Yin; Yue Jiang; Qingzhen Yang; Haishui Huang; Guangjun Nie; Hai Wang

doi:10.1002/adfm.202204636

Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy

Fuhao Jia, Wenping Huang, Yue Yin, Yue Jiang, Qingzhen Yang, Haishui Huang, Guangjun Nie, Hai Wang

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Massage RNA (mRNA) vaccines represent a new strategy for advanced cancer immunotherapy. To protect mRNA from degradation and deliver to targeted cells, lipid nanoparticles (LNPs) are extensively utilized as non-viral vectors. However, the stability of mRNA-laden LNPs substantially hinders their clinical application. Development of thermostable and durable mRNA nanovaccines is urgently needed. Here, a hyaluronan dynamic hydrogel is reported to protect mRNA and resiquimod (R848)-laden LNPs (HA-mRLNPs) from degradation at room temperature for durable cancer immunotherapy. A microfluidic device is proposed to effectively encapsulate mRNA and immunoadjuvants in LNPs (mRLNPs). Then, hyaluronan dynamic hydrogel is used to stabilize LNPs during storage at room temperature by restricting the migration and fusion of LNPs. Particularly, gel-like hyaluronan undergoes state transition for controlled release of mRLNPs under physiological condition. Therefore, HA-mRLNPs can efficiently deliver mRNA encoding tumor antigens to dendritic cells for antigen presentation to induce antigen-specific CD8⁺ T cells for killing tumor cells. Overall, this study demonstrates that the LNPs-hydrogel system can be used for effective cancer immunotherapy.

Original language	English (US)
Article number	2204636
Journal	Advanced Functional Materials
Volume	33
Issue number	3
DOIs	https://doi.org/10.1002/adfm.202204636
State	Published - Jan 16 2023

Keywords

hydrogels
immunotherapies
lipid nanoparticles
RNA nanovaccines

ASJC Scopus subject areas

Chemistry(all)
Materials Science(all)
Condensed Matter Physics

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title = "Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy",

abstract = "Massage RNA (mRNA) vaccines represent a new strategy for advanced cancer immunotherapy. To protect mRNA from degradation and deliver to targeted cells, lipid nanoparticles (LNPs) are extensively utilized as non-viral vectors. However, the stability of mRNA-laden LNPs substantially hinders their clinical application. Development of thermostable and durable mRNA nanovaccines is urgently needed. Here, a hyaluronan dynamic hydrogel is reported to protect mRNA and resiquimod (R848)-laden LNPs (HA-mRLNPs) from degradation at room temperature for durable cancer immunotherapy. A microfluidic device is proposed to effectively encapsulate mRNA and immunoadjuvants in LNPs (mRLNPs). Then, hyaluronan dynamic hydrogel is used to stabilize LNPs during storage at room temperature by restricting the migration and fusion of LNPs. Particularly, gel-like hyaluronan undergoes state transition for controlled release of mRLNPs under physiological condition. Therefore, HA-mRLNPs can efficiently deliver mRNA encoding tumor antigens to dendritic cells for antigen presentation to induce antigen-specific CD8+ T cells for killing tumor cells. Overall, this study demonstrates that the LNPs-hydrogel system can be used for effective cancer immunotherapy.",

keywords = "hydrogels, immunotherapies, lipid nanoparticles, RNA nanovaccines",

author = "Fuhao Jia and Wenping Huang and Yue Yin and Yue Jiang and Qingzhen Yang and Haishui Huang and Guangjun Nie and Hai Wang",

note = "Funding Information: This work was financially supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000), National Natural Science Foundation of China (31971307), and the Start-up Foundation of National Center for Nanoscience and Technology. The authors thank Core Facility of Center of Biomedical Analysis, Tsinghua University for assistance with Confocal Microscopy and Flow cytometry analysis. Funding Information: This work was financially supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000), National Natural Science Foundation of China (31971307), and the Start‐up Foundation of National Center for Nanoscience and Technology. The authors thank Core Facility of Center of Biomedical Analysis, Tsinghua University for assistance with Confocal Microscopy and Flow cytometry analysis. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

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doi = "10.1002/adfm.202204636",

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T1 - Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy

AU - Jia, Fuhao

AU - Huang, Wenping

AU - Yin, Yue

AU - Jiang, Yue

AU - Yang, Qingzhen

AU - Huang, Haishui

AU - Nie, Guangjun

AU - Wang, Hai

N1 - Funding Information: This work was financially supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000), National Natural Science Foundation of China (31971307), and the Start-up Foundation of National Center for Nanoscience and Technology. The authors thank Core Facility of Center of Biomedical Analysis, Tsinghua University for assistance with Confocal Microscopy and Flow cytometry analysis. Funding Information: This work was financially supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000), National Natural Science Foundation of China (31971307), and the Start‐up Foundation of National Center for Nanoscience and Technology. The authors thank Core Facility of Center of Biomedical Analysis, Tsinghua University for assistance with Confocal Microscopy and Flow cytometry analysis. Publisher Copyright: © 2022 Wiley-VCH GmbH.

PY - 2023/1/16

Y1 - 2023/1/16

N2 - Massage RNA (mRNA) vaccines represent a new strategy for advanced cancer immunotherapy. To protect mRNA from degradation and deliver to targeted cells, lipid nanoparticles (LNPs) are extensively utilized as non-viral vectors. However, the stability of mRNA-laden LNPs substantially hinders their clinical application. Development of thermostable and durable mRNA nanovaccines is urgently needed. Here, a hyaluronan dynamic hydrogel is reported to protect mRNA and resiquimod (R848)-laden LNPs (HA-mRLNPs) from degradation at room temperature for durable cancer immunotherapy. A microfluidic device is proposed to effectively encapsulate mRNA and immunoadjuvants in LNPs (mRLNPs). Then, hyaluronan dynamic hydrogel is used to stabilize LNPs during storage at room temperature by restricting the migration and fusion of LNPs. Particularly, gel-like hyaluronan undergoes state transition for controlled release of mRLNPs under physiological condition. Therefore, HA-mRLNPs can efficiently deliver mRNA encoding tumor antigens to dendritic cells for antigen presentation to induce antigen-specific CD8+ T cells for killing tumor cells. Overall, this study demonstrates that the LNPs-hydrogel system can be used for effective cancer immunotherapy.

AB - Massage RNA (mRNA) vaccines represent a new strategy for advanced cancer immunotherapy. To protect mRNA from degradation and deliver to targeted cells, lipid nanoparticles (LNPs) are extensively utilized as non-viral vectors. However, the stability of mRNA-laden LNPs substantially hinders their clinical application. Development of thermostable and durable mRNA nanovaccines is urgently needed. Here, a hyaluronan dynamic hydrogel is reported to protect mRNA and resiquimod (R848)-laden LNPs (HA-mRLNPs) from degradation at room temperature for durable cancer immunotherapy. A microfluidic device is proposed to effectively encapsulate mRNA and immunoadjuvants in LNPs (mRLNPs). Then, hyaluronan dynamic hydrogel is used to stabilize LNPs during storage at room temperature by restricting the migration and fusion of LNPs. Particularly, gel-like hyaluronan undergoes state transition for controlled release of mRLNPs under physiological condition. Therefore, HA-mRLNPs can efficiently deliver mRNA encoding tumor antigens to dendritic cells for antigen presentation to induce antigen-specific CD8+ T cells for killing tumor cells. Overall, this study demonstrates that the LNPs-hydrogel system can be used for effective cancer immunotherapy.

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KW - lipid nanoparticles

KW - RNA nanovaccines

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Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy

Abstract

Keywords

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