Inhibition of murine bladder cancer cell growth in vitro by photocontrollable siRNA based on upconversion fluorescent nanoparticles

PLoS One. 2014 Nov 25;9(11):e112713. doi: 10.1371/journal.pone.0112713. eCollection 2014.

Abstract

This study provides a unique approach to activate caged small interfering RNAs (siRNAs) using indirect UV light emitted by the near-infrared (NIR)-to-UV upconversion process to achieve high spatial and temporal gene interference patterns. siRNA molecules against the anti-apoptotic gene survivin was caged by light-sensitive molecules (4,5-dimethoxy-2-nitroacetophenone, DMNPE), which rendered them temporarily non-functional. NIR-to-UV NaYF4:Yb,Tm upconversion nanoparticles (UCPs) served as delivery vehicles and activators of the caged siRNA molecules in murine bladder cancer cells (MB49 cell line). Upconverted UV light at 355 nm was emitted from the NIR-irradiated UCPs, which well coincided with the wavelength needed to uncage DMNPE. Consequently, UV light acted as a switch to uncage the delivered siRNA molecule, thereby rendering fully functional for exerting its therapeutic effect in the bladder cancer cells. To achieve the highest RNA interference efficiency, conditions such as time after cellular uptake, excitation time, UCPs concentration and laser power were optimized. Results showed that 200 µg/mL nanoparticle concentration combined with 12 h incubation with MB49 cells and excitation with NIR laser at 100 mW power for 15 min provided the ideal interference efficiency and strongest induction of MB49 cell death. Our findings demonstrate the potential biological application of UCPs in treating bladder cancer by a novel therapeutic approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / radiation effects
  • Nitrobenzenes / chemistry
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Survivin
  • Ultraviolet Rays
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Nitrobenzenes
  • RNA, Small Interfering
  • Repressor Proteins
  • Survivin
  • 1-(4,5-dimethoxy-2-nitrophenyl)diazoethane

Grants and funding

This research was supported in part by grants from the National Natural Science Foundation of China (No. 31100688, No. 21471043), International Science & Technology Cooperation Program of China (No. 2014DFA31890), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, and the State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (SKLVEB2013KFKT010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.