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

Fuhao Jia; Wenping Huang; Yue YinYue JiangQingzhen YangHaishui HuangGuangjun NieHai Wang

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

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

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Massage RNA (mRNA) vaccines represent a new strategy for advancedcancer immunotherapy. To protect mRNA from degradation and deliver totargeted cells, lipid nanoparticles (LNPs) are extensively utilized as non-viralvectors. However, the stability of mRNA-laden LNPs substantially hinderstheir clinical application. Development of thermostable and durable mRNAnanovaccines is urgently needed. Here, a hyaluronan dynamic hydrogel isreported 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 andimmunoadjuvants in LNPs (mRLNPs). Then, hyaluronan dynamic hydrogelis used to stabilize LNPs during storage at room temperature by restrictingthe migration and fusion of LNPs. Particularly, gel-like hyaluronan undergoesstate transition for controlled release of mRLNPs under physiological condition.Therefore, HA-mRLNPs can efficiently deliver mRNA encoding tumorantigens to dendritic cells for antigen presentation to induce antigen-specificCD8~+ T cells for killing tumor cells. Overall, this study demonstrates that theLNPs-hydrogel system can be used for effective cancer immunotherapy.

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《Advanced functional materials》 |2023年第3期|2204636.1-2204636.12|共12页
作者
Fuhao Jia; Wenping Huang; Yue YinYue JiangQingzhen YangHaishui HuangGuangjun NieHai Wang;
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CAS Key Laboratory for Biomedical Effects of Nanomaterials &NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190, China, University of Chinese Academy of SciencesBeijing 100049, China;

Bioinspired Engineering and Biomechanics Center, The Key Laboratoryof Biomedical Information Engineering of Ministry of Education, Schoolof Life Science and TechnologyXi’an Jiaotong UniversityXi’an 710049, China;

CAS Key Laboratory for Biomedical Effects of Nanomaterials &NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190, China;

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正文语种英语
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hydrogels; immunotherapies; lipid nanoparticles; RNA nanovaccines;

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

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