Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging-Monitored Drug Delivery

Small. 2016 Nov;12(43):5944-5953. doi: 10.1002/smll.201601724. Epub 2016 Sep 20.

Abstract

Remote optical detection and imaging of specific tumor-related biomarkers and simultaneous activation of therapy according to the expression level of the biomarkers in tumor site with theranostic probes should be an effective modality for treatment of cancers. Herein, an upconversion nanobeacon (UCNPs-MB/Dox) is proposed as a new theranostic nanoprobe to ratiometrically detect and visualize the thymidine kinase 1 (TK1) mRNA that can simultaneously trigger the Dox release to activate the chemotherapy accordingly. UCNPs-MB/Dox is constructed with the conjugation of a TK1 mRNA-specific molecular beacon (MB) bearing a quencher (BHQ-1) and an alkene handle modified upconversion nanoparticle (UCNP) through click reaction and subsequently loading with a chemotherapy drug (Dox). With this nanobeacon, quantitative ratiometric upconversion detection of the target with high sensitivity and selectivity as well as the target triggered Dox release in vitro is demonstrated. The sensitive and selective ratiometric detection and imaging of TK1 mRNA under the irradiation of near infrared light (980 nm) and the mRNA-dependent release of Dox for chemotherapy in the tumor MCF-7 cells and A549 cells are also shown. This work provides a smart and robust platform for gene-related tumor theranostics.

Keywords: drug delivery; mRNA; molecular beacon; theranostic; upconversion nanoparticles.

MeSH terms

  • A549 Cells
  • Cell Death / drug effects
  • Diagnostic Imaging*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Fluorescence
  • Humans
  • MCF-7 Cells
  • Molecular Probes / chemistry*
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Theranostic Nanomedicine / methods*

Substances

  • Molecular Probes
  • RNA, Messenger
  • Doxorubicin