Supramolecularly Engineered Circular Bivalent Aptamer for Enhanced Functional Protein Delivery

作者：Ying Jiang, Xiaoshu Pan, Jin Chang, Weijia Niu, Weijia Hou, Hailan Kuai, Zilong Zhao, Ji Liu, Ming Wang, Weihong Tan · 发表于：Journal of the American Chemical Society · 年份：2018 · DOI：10.1021/jacs.8b03442 · 被引用次数：114 · 研究领域：Advanced biosensing and bioanalysis techniques、RNA Interference and Gene Delivery、DNA and Nucleic Acid Chemistry

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.