In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers
| Autor: | Kazuko Toh, Hiroaki Kinoh, Hiroyasu Takemoto, Mitsunobu R. Kano, Hiroshi Fukuhara, Sumiyo Watanabe, Keisuke Katsushima, Nobuhiro Nishiyama, Kotaro Hayashi, Yutaka Kondo, Hiroyuki Chaya, Satoshi Uchida, Satomi Ogura, Kanjiro Miyata, Takahiro Nomoto, Hyun Jin Kim, Horacio Cabral, Masaomi Nangaku, Kazunori Kataoka, Shigeto Fukushima, Shunya Uchida, Kensuke Osada, Xueying Liu, Yu Matsumoto, Hiroyoshi Y. Tanaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Small interfering RNA Oligonucleotides General Physics and Astronomy Cell Cycle Proteins 02 engineering and technology Polyethylene Glycols Mice Polylysine RNA Small Interfering lcsh:Science Regulation of gene expression Drug Carriers Multidisciplinary Brain Neoplasms Chemistry Carbocyanines 021001 nanoscience & nanotechnology Gene Expression Regulation Neoplastic medicine.anatomical_structure Injections Intravenous RNA Long Noncoding 0210 nano-technology Pancreas Science Static Electricity Antineoplastic Agents Protein Serine-Threonine Kinases Oligo delivery Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Targeted therapies In vivo Cell Line Tumor Proto-Oncogene Proteins medicine Animals Humans Fluorescent Dyes Oligonucleotide RNA General Chemistry Survival Analysis Xenograft Model Antitumor Assays Nanostructures Pancreatic Neoplasms 030104 developmental biology Cell culture Drug delivery Cancer research Nucleic acid lcsh:Q |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity. Nanoparticle delivery of siRNA has problems with penetration and off target accumulation. Here, the authors report on the development of Y-shaped block catiomers which dynamically wrap around siRNA; demonstrate increased circulation times and delivery into hard to reach brain and pancreas tumour models. |
| Databáze: | OpenAIRE |
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