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Updated: Sep 7, 2025

Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
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Calcium-Differentiated Cellular Internalization of Allosteric Framework Nucleic Acids for Targeted Payload Delivery

Jiao Zheng1, Qiwei Wang1, Lin Shi1

  • 1Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.

Analytical Chemistry
|June 16, 2022
PubMed

Insights

This study introduces a novel cancer-targeting delivery system using framework nucleic acids (FNAs) that transform in response to the tumor microenvironment. This smart nanovehicle enhances cellular uptake and enables precise mRNA imaging for targeted cancer therapy.

Area of Science:

  • Biochemistry
  • Nanotechnology
  • Molecular Biology

Background:

  • Targeted delivery systems are crucial for effective cancer therapy.
  • Smart nanocarriers that respond to the tumor microenvironment offer improved specificity.
  • Framework nucleic acids (FNAs) present a versatile platform for nanomedicine development.

Purpose of the Study:

  • To engineer a novel allosteric FNA nanovehicle for targeted cancer cell delivery.
  • To utilize Ca2+-differentiated cellular internalization for enhanced nanovehicle uptake.
  • To develop a new system for live-cell mRNA imaging and targeted drug delivery.

Main Methods:

  • Construction of an allosteric FNA nanovehicle.
  • Induction of 2D-to-3D FNA transformation via G-quadruplexes responding to K+.
  • Demonstration of Ca2+-promoted cellular internalization.
  • Delivery of antisense strand cargo for mRNA imaging.

Main Results:

  • The FNA nanovehicle undergoes a 2D-to-3D structural transformation on the cancer cell surface.
  • G-quadruplexes respond to extracellular K+, facilitating the transformation.
  • Ca2+ significantly enhances the cellular internalization of the transformed FNA nanovehicle.
  • Successful delivery of antisense cargo for live-cell mRNA imaging was achieved.

Conclusions:

  • A new class of allosteric FNA nanovehicles has been developed for targeted cancer therapy.
  • The Ca2+-differentiated internalization mechanism enhances delivery efficiency.
  • This platform opens new avenues for precise disease treatment and targeted drug delivery.

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