Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 140, Issue 22, Pages 6780-6784Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b03442
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Funding
- NSFC [21521063, 21778056, 21405041]
- NIH [GM R35 127130, NSF 1645215]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R35GM127130] Funding Source: NIH RePORTER
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Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a beta-cyclodextrin-modified cb-apt (cb-apt-beta CD) and its supramolecular interaction with molecular therapeutics via host guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer. The cb-apt-beta CD ensemble delivers green fluorescent protein into targeted cells with efficiency as high as 80%, or cytotoxic saporin to efficiently inhibit tumor cell growth. The strategy of conjugating beta CD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-beta CD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.
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