Programmable Metal/Semiconductor Nanostructures for mRNA-Modulated Molecular Delivery

Libing Zhang, Sae Rin Jean, Xiyan Li, Tanja Sack, Zongjie Wang, Sharif Ahmed, Gordon Chan, Jagotamoy Das, Alexandre Zaragoza, Edward H. Sargent, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Cytotoxic chemotherapeutics are important tools for the clinical treatment of a variety of solid tumors. However, their use is often complicated by multidrug resistance that can develop in patients, limiting the potencies of these agents. New strategies are needed to provide versatile systems that can respond to and disable resistance mechanisms. We demonstrate the use of a new family of materials, programmable metal/semiconductor nanostructures, for drug delivery and mRNA sensing in drug-resistant cells. These materials are composed of a central core gold nanoparticle surrounded by a layer of DNA-capped quantum dots. The modularity of these "core-satellite" assemblies allows for the construction of superstructures with controlled size and the incorporation of multiple functionalities for drug delivery. The DNA sequence within the nanoparticle specifically binds to an mRNA encoding an important drug resistance factor, MRP1, inside cancer cells, releasing a potent anticancer drug doxorubicin. This event triggers a turn-on fluorescence emission along with a downregulation of the MRP1 drug efflux pump, a main resistance factor for doxorubicin, yielding a remarkable improvement in therapeutic efficacy against drug-resistant cancer cells. This work paves the way for the development of programmable materials with multiple synergistic functionalities for biomedical applications.

Original languageEnglish (US)
Pages (from-to)6222-6228
Number of pages7
JournalNano letters
Volume18
Issue number10
DOIs
StatePublished - Oct 10 2018

Keywords

  • DNA
  • mRNA
  • multidrug resistance
  • quantum dots
  • Self-assembly

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Fingerprint

Dive into the research topics of 'Programmable Metal/Semiconductor Nanostructures for mRNA-Modulated Molecular Delivery'. Together they form a unique fingerprint.

Cite this