Novel bionic inspired nanosystem construction for precise delivery of mRNA

Taihua Yang; Lei Xia; Gen Li; Jie Zhao; Jie Li; Jiahao Ge; Qinggong Yuan; Jianjun Zhang; Kang He; Qiang Xia

doi:10.3389/fbioe.2023.1160509

Novel bionic inspired nanosystem construction for precise delivery of mRNA

Front Bioeng Biotechnol. 2023 Mar 2:11:1160509. doi: 10.3389/fbioe.2023.1160509. eCollection 2023.

Authors

Taihua Yang¹, Lei Xia¹, Gen Li², Jie Zhao¹, Jie Li¹, Jiahao Ge¹, Qinggong Yuan³, Jianjun Zhang¹, Kang He¹, Qiang Xia^{1

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Affiliations

¹ Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
⁴ Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, China.
⁵ Shanghai Institute of Transplantation, Shanghai, China.

Abstract

The intracellular delivery of messenger (m)RNA holds great potential for the discovery and development of vaccines and therapeutics. Yet, in many applications, a major obstacle to clinical translation of mRNA therapy is the lack of efficient strategy to precisely deliver RNA sequence to liver tissues and cells. In this study, we synthesized virus-like mesoporous silica (V-SiO₂) nanoparticles for effectively deliver the therapeutic RNA. Then, the cationic polymer polyethylenimine (PEI) was included for the further silica surface modification (V-SiO₂-P). Negatively charged mRNA motifs were successfully linked on the surface of V-SiO₂ through electrostatic interactions with PEI (m@V-SiO₂-P). Finally, the supported lipid bilayer (LB) was completely wrapped on the bionic inspired surface of the nanoparticles (m@V-SiO₂-P/LB). Importantly, we found that, compared with traditional liposomes with mRNA loading (m@LNPs), the V-SiO₂-P/LB bionic-like morphology effectively enhanced mRNA delivery effect to hepatocytes both in vitro and in vivo, and PEI modification concurrently promoted mRNA binding and intracellular lysosomal escape. Furthermore, m@V-SiO₂-P increased the blood circulation time (t_1/2 = 7 h) to be much longer than that of the m@LNPs (4.2 h). Understanding intracellular delivery mediated by the V-SiO₂-P/LB nanosystem will inspire the next-generation of highly efficient and effective mRNA therapies. In addition, the nanosystem can also be applied to the oral cavity, forehead, face and other orthotopic injections.

Keywords: bionic inspired nanosystem; liver target; oral in Situ injection; precise delivery of mRNA; virus-like mesoporous silica.

Grants and funding

This work was supported by grants from the China Postdoctoral Science Foundation (No. 2021M702180), the National Natural Science Foundation of China (82102618), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (20204Y0351), the Shanghai Science and Technology Development Funds (No. 22YF1423900), the Nucleic Acid Drug Project of the National Biopharmaceutical Technology Innovation Center (No. NCTIB2022HS02004), the National and provincial multidisciplinary cooperative diagnosis and treatment capacity building project for major diseases (82241221), and the National key project, special project of medical innovation research of Shanghai “Science and Technology Innovation Action Plan” (22Y21900400).