Frontiers in Bioengineering and Biotechnology (Aug 2022)

RETRACTED: Multicomponent siRNA/miRNA-loaded modified mesoporous silica nanoparticles targeted bladder cancer for a highly effective combination therapy

  • Maryamsadat Shahidi,
  • Omid Abazari,
  • Parisa Dayati,
  • Ali Bakhshi,
  • Javad Zavarreza,
  • Mohammad Hossein Modarresi,
  • Fateme Haghiralsadat,
  • Mehdi Rahmanian,
  • Seyed Morteza Naghib,
  • Davood Tofighi

DOI
https://doi.org/10.3389/fbioe.2022.949704
Journal volume & issue
Vol. 10

Abstract

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Bladder cancer is one of the concerning urological malignant diseases in the world, which has a clinical need for effective targeted therapy. The development of nanotechnology-based gene delivery to bladder tumor sites is an effective strategy for targeted cancer therapy with low/no toxicity. With this view, in the present work, the mesoporous silica nanoparticles (MSNs) modified with c(RGDfK)-PLGA-PEG [c(RGDfK)-MSN NPs] were constructed for co-delivery of miR-34a and siPD-L1 within bladder cancer cells and tissues. Our findings showed that miR-34a is downregulated while PD-L1 is up-regulated in cell lines and animal studies. This nano-carrier is biocompatible in the serum environment and effectively protects miR-34a and siPD-L1 against serum degradation. However, we showed that c(RGDfK)-MSN NPs could simultaneously downregulate PD-L1 expression and up-regulate miR-34a in the T24 cells and T24 mice model and enhance anti-tumor effects both in vivo and in vitro. In conclusion, these findings presented new suggestions for improving targeted therapeutic strategies with specified molecular objectives for bladder cancer treatment.

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