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 2024-01-19T17:04:32Z 2024-01-19T17:04:32Z 2021-09-05 2020-07 1999-4923 https://pubs.kist.re.kr/handle/201004/118462 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. English MDPI DNA APTAMER NUCLEOLIN AS1411 THERAPY OLIGONUCLEOTIDES NANOPARTICLES CHEMOTHERAPY AGENT Combinatorial Inhibition of Cell Surface Receptors Using Dual Aptamer-Functionalized Nanoconstructs for Cancer Treatment Article 10.3390/pharmaceutics12070689 1 PHARMACEUTICS, v.12, no.7 PHARMACEUTICS 12 7 scie scopus 000554212800001 2-s2.0-85088276178 Pharmacology & Pharmacy Pharmacology & Pharmacy Article DNA APTAMER NUCLEOLIN AS1411 THERAPY OLIGONUCLEOTIDES NANOPARTICLES CHEMOTHERAPY AGENT combinatorial treatment aptamer gold nanoconstructs surface receptor receptor interaction