In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers

Sumiyo Watanabe, Kotaro Hayashi, Kazuko Toh, Hyun Jin Kim, Xueying Liu, Hiroyuki Chaya, Shigeto Fukushima, Keisuke Katsushima, Yutaka Kondo, Satoshi Uchida, Satomi Ogura, Takahiro Nomoto, Hiroyasu Takemoto, Horacio Cabral, Hiroaki Kinoh, Hiroyoshi Y. Tanaka, Mitsunobu R. Kano, Yu Matsumoto, Hiroshi Fukuhara, Shunya Uchida, Masaomi Nangaku, Kensuke Osada, Nobuhiro Nishiyama, Kanjiro Miyata () and Kazunori Kataoka ()
Additional contact information
Sumiyo Watanabe: The University of Tokyo
Kotaro Hayashi: Kawasaki Institute of Industrial Promotion
Kazuko Toh: Kawasaki Institute of Industrial Promotion
Hyun Jin Kim: The University of Tokyo
Xueying Liu: Kawasaki Institute of Industrial Promotion
Hiroyuki Chaya: The University of Tokyo
Shigeto Fukushima: Kawasaki Institute of Industrial Promotion
Keisuke Katsushima: Nagoya University Graduate School of Medicine
Yutaka Kondo: Nagoya University Graduate School of Medicine
Satoshi Uchida: The University of Tokyo
Satomi Ogura: Kawasaki Institute of Industrial Promotion
Takahiro Nomoto: Tokyo Institute of Technology
Hiroyasu Takemoto: Tokyo Institute of Technology
Horacio Cabral: The University of Tokyo
Hiroaki Kinoh: Kawasaki Institute of Industrial Promotion
Hiroyoshi Y. Tanaka: Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Mitsunobu R. Kano: Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Yu Matsumoto: The University of Tokyo
Hiroshi Fukuhara: Kyorin University Faculty of Medicine
Shunya Uchida: Teikyo University School of Medicine
Masaomi Nangaku: The University of Tokyo
Kensuke Osada: The University of Tokyo
Nobuhiro Nishiyama: Tokyo Institute of Technology
Kanjiro Miyata: The University of Tokyo
Kazunori Kataoka: Kawasaki Institute of Industrial Promotion

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09856-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09856-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09856-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().