Extracellular Ion-Responsive Logic Sensors Utilizing DNA Dimeric Nanoassemblies on Cell Surface and Application to Boosting AS1411 Internalization

Analytical Chemistry
Pai PengTao Li

Abstract

High levels of extracellular H+ and K+ are unique features of the tumor microenvironment and have shown great promise for use in cancer-targeted drug delivery. Here, we design H+- and/or K+-responsive logic sensors utilizing in situ dimeric framework nucleic acid (FNA) assembly on the cell surface and for the first time apply the logic sensors to boosting cellular internalization of molecular payloads in tumor-mimicking extracellular environments. An anticancer aptamer AS1411 is blocked on branched FNA vertexes where a bimolecular i-motif is tethered as the controlling unit to enable a dimeric DNA nanoassembly in response to extracellular pH change. K+ promotes AS1411 to fold into a G-quadruplex and thereby release from dimeric FNA in which a proximity DNA hybridization-based FRET happens. Furthermore, such an AND-gated nanosensor functions more efficiently for AS1411 internalization than the conventional pathway. This finding shows significant implications for tumor-microenvironment-recognizing target drug delivery and precision cancer therapy.

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Citations

Nov 18, 2020·The Journal of Membrane Biology·Anjali RajwarDhiraj Bhatia
Aug 28, 2021·Analytical Chemistry·Jingxin LiuShuangchen Ruan
Jan 7, 2022·Angewandte Chemie·Wen Yi LvCheng Zhi Huang

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