AUTHOR=Shahidi Maryamsadat , Abazari Omid , Dayati Parisa , Bakhshi Ali , Zavarreza Javad , Modarresi Mohammad Hossein , Haghiralsadat Fateme , Rahmanian Mehdi , Naghib Seyed Morteza , Tofighi Davood TITLE=Multicomponent siRNA/miRNA-loaded modified mesoporous silica nanoparticles targeted bladder cancer for a highly effective combination therapy JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.949704 DOI=10.3389/fbioe.2022.949704 ISSN=2296-4185 ABSTRACT=

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.