The Effect of Cholesterol Content on the Adjuvant Activity of Nucleic-Acid-Free Lipid Nanoparticles

被引：4

作者：

Anindita, Jessica ^{[1
,2
]}

Tanaka, Hiroki ^{[1
,3
,4
]}

Yamakawa, Takuma ^{[2
]}

Sato, Yuka ^{[2
]}

Matsumoto, Chika ^{[1
]}

Ishizaki, Kota ^{[2
]}

Oyama, Taiji ^{[5
]}

Suzuki, Satoko ^{[6
]}

Ueda, Keisuke ^{[7
]}

Higashi, Kenjirou ^{[7
]}

Moribe, Kunikazu ^{[7
]}

Sasaki, Kasumi ^{[8
]}

Ogura, Yumika ^{[8
]}

Yonemochi, Etsuo ^{[8
]}

Sakurai, Yu ^{[1
]}

Hatakeyama, Hiroto ^{[2
]}

Akita, Hidetaka ^{[1
,3
,4
]}

机构：

[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Lab DDS Design & Drug Disposit, 6-3 Aoba Aramaki,Aoba Ku, Sendai, Miyagi 9808578, Japan

[2] Chiba Univ, Grad Sch Pharmaceut Sci, Lab DDS Design & Drug Disposit, 1-8-1 Inohana,Chuo Ku, Chiba, Chiba 2600856, Japan

[3] Osaka Univ, Ctr Adv Modal, Suita, Osaka 5650871, Japan

[4] Osaka Univ, DDS, Suita, Osaka 5650871, Japan

[5] JASCO Corp, Sales Div, 2967-5 Ishikawa, Hachioji, Tokyo 1928537, Japan

[6] JASCO Corp, Applicat Solut Lab Div, 2967-5 Ishikawa, Hachioji, Tokyo 1928537, Japan

[7] Chiba Univ, Grad Sch Pharmaceut Sci, Lab Pharmaceut Technol, 1-8-1 Inohana,Chuo Ku, Chiba, Chiba 2600856, Japan

[8] Hoshi Univ, Sch Pharm & Pharmaceut Sci, Dept Phys Chem, 2-4-41 Ebara,Shinagawa Ku, Shinagawa, Tokyo 1428501, Japan

来源：

PHARMACEUTICS | 2024年 / 16卷 / 02期

关键词：

lipid nanoparticle; cholesterol; particle morphology; adjuvant activity; MESSENGER-RNA; CRYSTAL-STRUCTURE; PROTEIN EXPRESSION; INNATE; PHASE; CELL; PSEUDOURIDINE; RESPONSES; SHAPE;

D O I：

10.3390/pharmaceutics16020181

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.

引用

页数：16

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