The impact of, and expectations for, lipid nanoparticle technology: From cellular targeting to organelle targeting

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY Journal of Controlled Release Pub Date : 2024-05-09 DOI:10.1016/j.jconrel.2024.05.006

Yusuke Sato, Takashi Nakamura, Yuma Yamada, Hideyoshi Harashima

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Abstract

The success of mRNA vaccines against COVID-19 has enhanced the potential of lipid nanoparticles (LNPs) as a system for the delivery of mRNA. In this review, we describe our progress using a lipid library to engineer ionizable lipids and promote LNP technology from the viewpoints of safety, controlled biodistribution, and mRNA vaccines. These advancements in LNP technology are applied to cancer immunology, and a potential nano-DDS is constructed to evaluate immune status that is associated with a cancer-immunity cycle that includes the sub-cycles in tumor microenvironments. We also discuss the importance of the delivery of antigens and adjuvants in enhancing the cancer-immunity cycle. Recent progress in NK cell targeting in cancer immunotherapy is also introduced. Finally, the impact of next-generation DDS technology is explained using the MITO-Porter membrane fusion-based delivery system for the organelle targeting of the mitochondria. We introduce a successful example of the MITO-Porter used in a cell therapeutic strategy to treat cardiomyopathy.

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脂质纳米粒子技术的影响和期望：从细胞靶向到细胞器靶向。

针对 COVID-19 的 mRNA 疫苗的成功提高了脂质纳米颗粒 (LNP) 作为一种 mRNA 递送系统的潜力。在这篇综述中，我们介绍了利用脂质库来设计可离子化脂质的进展，并从安全性、可控生物分布和 mRNA 疫苗的角度来推广 LNP 技术。我们将 LNP 技术的这些进展应用于癌症免疫学，并构建了一种潜在的纳米 DDS，用于评估与癌症免疫周期（包括肿瘤微环境中的子周期）相关的免疫状态。我们还讨论了输送抗原和佐剂在增强癌症免疫循环中的重要性。我们还介绍了癌症免疫疗法中 NK 细胞靶向治疗的最新进展。最后，我们使用基于 MITO-Porter 膜融合的递送系统来解释下一代 DDS 技术对线粒体细胞器靶向的影响。我们介绍了 MITO-Porter 用于治疗心肌病的细胞治疗策略的一个成功实例。

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.