Journal
PHARMACEUTICS
Volume 12, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics12070689
Keywords
combinatorial treatment; aptamer; gold nanoconstructs; surface receptor; receptor interaction
Categories
Funding
- KIST Institutional Program [2E30341]
- National Research Foundation of Korea (NRF) - Korea government [2020R1C1C1009507, NRF-2016R1A6A3A04009677]
- Nano.Material Technology Development Program through the National Research Foundation of Korea - Ministry of Science and ICT [NRF2018M3A7B4071106]
- National Research Foundation of Korea [2020R1C1C1009507] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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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