Inulin coated Mn 3 O 4 nanocuboids coupled with RNA interference reverse intestinal tumorigenesis in Apc knockout murine colon cancer models

This study reports the development and pre-clinical evaluation of biodrug using RNA interference and nanotechnology. The major challenges in achieving targeted gene silencing in vivo include the stability of RNA molecules, accumulation into pharmacological levels, and site-specific targeting of the...

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Bibliographic Details
Published inNanomedicine Vol. 40; p. 102504
Main Authors Kourani, Khushboo, Jain, Poonam, Kumar, Aviral, Jangid, Ashok Kumar, Swaminathan, Guruprasadh, Durgempudi, Varsha Reddy, Jose, Jedy, Reddy, Rithvik, Pooja, Deep, Kulhari, Hitesh, Kumar, Lekha Dinesh
Format Journal Article
LanguageEnglish
Published United States 01.02.2022
Subjects
Animals
Carcinogenesis
Colonic Neoplasms - drug therapy
Colonic Neoplasms - genetics
Inulin
Mice
Mice, Knockout
RNA Interference
RNA, Small Interfering - therapeutic use
Nanocuboids
RNAi
Apc knockout models
Ephb4 shRNA
Colorectal cancer
Manganese oxide
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Summary:This study reports the development and pre-clinical evaluation of biodrug using RNA interference and nanotechnology. The major challenges in achieving targeted gene silencing in vivo include the stability of RNA molecules, accumulation into pharmacological levels, and site-specific targeting of the tumor. We report the use of Inulin for coating the arginine stabilized manganese oxide nanocuboids (MNCs) for oral delivery of shRNA to the gut. Furthermore, bio-distribution analysis exhibited site-specific targeting in the intestines, improved pharmacokinetic properties, and faster elimination from the system without cytotoxicity. To evaluate the therapeutic possibility and effectiveness of this multimodal bio-drug, it was orally delivered to Apc knockout colon cancer mice models. Persistent and efficient delivery of bio-drug was demonstrated by the knockdown of target genes and increased median survival in the treated cohorts. This promising utility of RNAi-Nanotechnology approach advocates the use of bio-drug in an effort to replace chemo-drugs as the future of cancer therapeutics.
ISSN:1549-9642