Calcium-Differentiated Cellular Internalization of Allosteric Framework Nucleic Acids for Targeted Payload Delivery.

Target delivery systems have extensively shown promising applications in cancer therapy, and many of them function smartly by responding to the cancer cell microenvironment. Here, we for the first time report Ca 2+ -differentiated cellular internalization of 2D/3D framework nucleic acids (FNAs), enabling the engineering of a conceptually new target delivery system using an allosteric FNA nanovehicle. The FNA vehicle is subject to a 2D-to-3D transformation on the cancer cell surface via G-quadruplexes responding to environmental K + and thereby allows its cell entry to be more efficiently promoted by Ca 2+ . This design enables the FNA vehicle to target cancer cells and selectively deliver an antisense strand-containing cargo for live-cell mRNA imaging. It would open new avenues toward targeted drug delivery and find extensive applications in precise disease treatment.