期刊
JOURNAL OF CONTROLLED RELEASE
卷 330, 期 -, 页码 305-316出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.12.032
关键词
LNP; Ionizable amino lipid; Nanomedicine; Cancer immunotherapy; Adjuvant; Endosomal escape; Mitochondrial gene therapy; MEND; MITO-porter
资金
- Ministry of Education, Culture, Sports, Science and Technology [19H01170, 20H04523, 20H03373, 18K19888, 18K19889]
- Japanese Government (MEXT)
- Uehara Memorial Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [20H03373, 20H04523, 18K19889, 18K19888, 19H01170] Funding Source: KAKEN
The era of nanomedicine has arrived, with lipid nanoparticle (LNP) technology successfully delivering siRNA to treat genetic diseases and COVID-19 mRNA vaccines. New lipids for LNP formulations and mechanisms of targeting without ligands are discussed. Clinical applications of nano DDS in cancer immunology and new cancer therapy targeting mitochondria are also highlighted.
The era of Nanomedicine has arrived with the approval of ONPATTRO (TM) by the FDA in 2018. Lipid nanoparticle (LNP) technology has succeeded in delivering siRNA to the human liver in genetic diseases and has also been applied to mRNA vaccinations for COVID-19 using a similar LNP technology. In this review, we focus on the current status of new lipids for use in LNP formulations including our original lipids (CL4H6/CL4C6/CL4D6) as well as mechanisms of targeting without a ligand. Clinical applications of nano DDS are moving forward rapidly in the field of cancer immunology since the successful introduction of OPDIVO (TM) in 2014. Antigen presentation and the maturation of immune cells can be controlled by nano DDS for cancer immunotherapy. YSK12-C4, a newly designed ionizable amino lipid can induce successful immune activation by silencing mRNA in DC and NK cells, which are expected to be evaluated for clinical use. Finally, new cancer therapy by targeting mitochondria involving the use of a MITO-Porter, a membrane fusion-type mitochondrial delivery system, has been introduced. The importance of delivering a photo sensitizer to mitochondria was clearly demonstrated in photodynamic cancer therapy. Clinical applications of MITO-Porters started in collaborative efforts with LUCA Science Co., Ltd. And was established in 2018. The future direction of Nanomedicine is discussed.
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