A mechanistic study on the cellular uptake, intracellular trafficking, and antisense gene regulation of bottlebrush polymer-conjugated oligonucleotides

Author:

Zhang Lei12,Wang Yuyan2,Chen Peiru2,Wang Dali2,Sun Tingyu2,Zhang Zheyu2,Wang Ruimeng2,Kang Xi2ORCID,Fang Yang2,Lu Hao2,Cai Jiansong2,Ren Mengqi2,Dong Sijia S.2ORCID,Zhang Ke23ORCID

Affiliation:

1. Chemicobiology and Functional Materials Institute, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China

2. Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA

3. Departments of Chemical Engineering and Bioengineering, Northeastern University, Boston, Massachusetts 02115, USA

Abstract

We show that a bottlebrush polymer-antisense oligonucleotide conjugate (termed pacDNA) enters cancer cells by scavenger receptor-mediated endocytosis and micropinocytosis, trafficks via the endolysosomal pathway, and functions as a steric blocker.

Funder

National Cancer Institute

National Institute of General Medical Sciences

National Science Foundation

Publisher

Royal Society of Chemistry (RSC)

Subject

Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Biology,Biochemistry,Chemistry (miscellaneous)

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