Combinatorial Inhibition of Cell Surface Receptors Using Dual Aptamer-Functionalized Nanoconstructs for Cancer Treatment
- Authors
- Lee, Hyojin; Kim, Tae Hee; Park, Daechan; Jang, Mihue; Chung, Justin J.; Kim, Soo Hyun; Kim, Sang-Heon; Lee, Kwan Hyi; Jung, Youngmee; Oh, Seung Ja
- Issue Date
- 7월-2020
- Publisher
- MDPI
- Keywords
- combinatorial treatment; aptamer; gold nanoconstructs; surface receptor; receptor interaction
- Citation
- PHARMACEUTICS, v.12, no.7
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACEUTICS
- Volume
- 12
- Number
- 7
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/54497
- DOI
- 10.3390/pharmaceutics12070689
- ISSN
- 1999-4923
- Abstract
- Membrane receptors overexpressed in diseased states are considered novel therapeutic targets. However, the single targeting approach faces several fundamental issues, such as poor efficacy, resistance, and toxicity. Here, we report a dual-targeting strategy to enhance anti-cancer efficacy via synergistic proximity interactions between therapeutics and two receptor proteins. Importantly, we report the first finding of an interaction between c-Met and nucleolin and demonstrate the therapeutic value of targeting the interaction between them. Bispecific nanocarriers densely grafted with anti-c-Met and -nucleolin aptamer increased the local concentration of aptamers at the target sites, in addition to inducing target receptor clustering. It was also demonstrated that the simultaneous targeting of c-Met and nucleolin inhibited the cellular functions of the receptors and increased anti-cancer efficacy by altering the cell cycle. Our findings pave the way for the development of an effective combinatorial treatment based on nanoconstruct-mediated interaction between receptors.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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