Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Aptamer Engineering Center of Hunan Province , Hunan University , Changsha , Hunan 410082 , People's Republic of China.
Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute , University of Florida , Gainesville , Florida 32611-7200 , United States.
J Am Chem Soc. 2018 Jun 6;140(22):6780-6784. doi: 10.1021/jacs.8b03442. Epub 2018 May 24.
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.
环状二价适体（cb-apt）是一类新兴的化学工程适体，具有显著提高的稳定性和分子识别能力。然而，由于缺乏控制 cb-apt 与治疗剂相互作用的功能模块，其治疗应用受到挑战。我们提出了一种β-环糊精修饰的 cb-apt（cb-apt-βCD）的设计，并通过主客体化学研究了其与分子治疗剂的超分子相互作用，以实现靶向细胞内递药。与单体适体相比，超分子聚集体表现出更高的血清稳定性和增强的细胞内递药效率。cb-apt-βCD 聚集体能够高效地将绿色荧光蛋白递送到靶细胞中，效率高达 80%，或递送到靶细胞中具有细胞毒性的丝裂霉素 S，从而有效地抑制肿瘤细胞生长。将βCD 与 cb-apt 缀合，随后调节 cb-apt-βCD 的超分子化学，为扩展和多样化适体的功能提供了一个通用平台，从而实现新的生物学和治疗应用。
