Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Laboratory for Biological Drug Development based on DDS Technology, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
J Control Release. 2021 Feb 10;330:305-316. doi: 10.1016/j.jconrel.2020.12.032. Epub 2020 Dec 20.
The era of Nanomedicine has arrived with the approval of ONPATTRO™ 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™ 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.
2018 年，FDA 批准 ONPATTRO™上市，标志着纳米医学时代的到来。脂质纳米颗粒（LNP）技术已成功将 siRNA 递送至人类肝脏中的遗传疾病，并已应用于使用类似 LNP 技术的 COVID-19 mRNA 疫苗。在这篇综述中，我们重点介绍了新型 LNP 制剂用脂质的现状，包括我们的原创脂质（CL4H6/CL4C6/CL4D6）以及无配体靶向的机制。自 2014 年 OPDIVO™成功推出以来，纳米 DDS 在癌症免疫学领域的临床应用迅速推进。纳米 DDS 可控制抗原呈递和免疫细胞的成熟，用于癌症免疫治疗。YSK12-C4 是一种新设计的可离子化氨基酸脂质，通过沉默 DC 和 NK 细胞中的 mRNA 可以诱导成功的免疫激活，有望进行临床评估。最后，介绍了一种新型的靶向线粒体的癌症治疗方法，涉及使用膜融合型线粒体递药系统 MITO-Porter。光动力癌症治疗清楚地表明了将光增敏剂递送至线粒体的重要性。MITO-Porters 的临床应用始于与 LUCA Science Co., Ltd. 的合作，并于 2018 年建立。讨论了纳米医学的未来方向。
