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

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 tu...

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Autores principales: Xin Wu, Yuhki Yokoyama, Hidekazu Takahashi, Shihori Kouda, Hiroyuki Yamamoto, Jiaqi Wang, Yoshihiro Morimoto, Kazumasa Minami, Tsuyoshi Hata, Awad Shamma, Akira Inoue, Masahisa Ohtsuka, Satoshi Shibata, Shogo Kobayashi, Shuji Akai, Hirofumi Yamamoto
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/e7e544c360f24339ba9edac8c7656425
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spelling oai:doaj.org-article:e7e544c360f24339ba9edac8c76564252021-11-25T18:07:38ZImproved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method10.3390/jpm111111602075-4426https://doaj.org/article/e7e544c360f24339ba9edac8c76564252021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1160https://doaj.org/toc/2075-4426In 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.Xin WuYuhki YokoyamaHidekazu TakahashiShihori KoudaHiroyuki YamamotoJiaqi WangYoshihiro MorimotoKazumasa MinamiTsuyoshi HataAwad ShammaAkira InoueMasahisa OhtsukaSatoshi ShibataShogo KobayashiShuji AkaiHirofumi YamamotoMDPI AGarticleiNaDsiRNAmicroRNAcalcium phosphatePEG blendingcancer treatmentMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1160, p 1160 (2021)
institution DOAJ
collection DOAJ
language EN
topic iNaD
siRNA
microRNA
calcium phosphate
PEG blending
cancer treatment
Medicine
R
spellingShingle iNaD
siRNA
microRNA
calcium phosphate
PEG blending
cancer treatment
Medicine
R
Xin Wu
Yuhki Yokoyama
Hidekazu Takahashi
Shihori Kouda
Hiroyuki Yamamoto
Jiaqi Wang
Yoshihiro Morimoto
Kazumasa Minami
Tsuyoshi Hata
Awad Shamma
Akira Inoue
Masahisa Ohtsuka
Satoshi Shibata
Shogo Kobayashi
Shuji Akai
Hirofumi Yamamoto
Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
description 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.
format article
author Xin Wu
Yuhki Yokoyama
Hidekazu Takahashi
Shihori Kouda
Hiroyuki Yamamoto
Jiaqi Wang
Yoshihiro Morimoto
Kazumasa Minami
Tsuyoshi Hata
Awad Shamma
Akira Inoue
Masahisa Ohtsuka
Satoshi Shibata
Shogo Kobayashi
Shuji Akai
Hirofumi Yamamoto
author_facet Xin Wu
Yuhki Yokoyama
Hidekazu Takahashi
Shihori Kouda
Hiroyuki Yamamoto
Jiaqi Wang
Yoshihiro Morimoto
Kazumasa Minami
Tsuyoshi Hata
Awad Shamma
Akira Inoue
Masahisa Ohtsuka
Satoshi Shibata
Shogo Kobayashi
Shuji Akai
Hirofumi Yamamoto
author_sort Xin Wu
title Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
title_short Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
title_full Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
title_fullStr Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
title_full_unstemmed Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method
title_sort improved in vivo delivery of small rna based on the calcium phosphate method
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/e7e544c360f24339ba9edac8c7656425
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