Supramolecularly Engineered Circular Bivalent Aptamer for Enhanced Functional Protein Delivery

Journal of the American Chemical Society
Ying JiangWeihong Tan

Abstract

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 β-cyclodextrin-modified cb-apt (cb-apt-βCD) 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-βCD 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 βCD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-βCD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.

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Citations

Sep 27, 2018·Chemical Communications : Chem Comm·X ZhouJ Jayawickramarajah
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Feb 6, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Pi DingRenjun Pei
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