基于磷酸钙法的小RNA体内递送效果的改善

Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method.

作者信息

Wu Xin, Yokoyama Yuhki, Takahashi Hidekazu, Kouda Shihori, Yamamoto Hiroyuki, Wang Jiaqi, Morimoto Yoshihiro, Minami Kazumasa, Hata Tsuyoshi, Shamma Awad, Inoue Akira, Ohtsuka Masahisa, Shibata Satoshi, Kobayashi Shogo, Akai Shuji, Yamamoto Hirofumi

机构信息

Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

出版信息

J Pers Med. 2021 Nov 8;11(11):1160. doi: 10.3390/jpm11111160.

DOI:10.3390/jpm11111160

PMID:34834512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8623677/

Abstract

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

摘要

在过去几年中，我们已经证明了一种纳米颗粒系统——超碳酸盐磷灰石（sCA）用于体内递送siRNA/miRNA的有效性。静脉注射负载小RNA的sCA在小鼠模型中可实现安全、高效的肿瘤递送。为了进一步提高肿瘤递送效率并避免肝脏毒性，我们在生产sCA的过程中，通过高频超声粉碎结合聚乙二醇（PEG）混合，成功开发了一种无机纳米颗粒装置（iNaD）。与负载24μg miRNA的sCA相比，全身给药负载0.75μg miRNA的iNaD对小鼠肿瘤的递送效率相似，且在肝脏中的积累很少。在小鼠治疗模型中，与负载24μg的sCA相比，负载3μg肿瘤抑制小RNA MIRTX的iNaD具有更好的抗肿瘤效果。我们关于iNaD生物分布和治疗效果的研究结果为未来的纳米医学工程提供了新的视角。