Multicomponent Sirna/Mirna-Loaded Modified Mesoporous Silica Nanoparticles Targeted Bladder Cancer for a Highly Effective Combination Therapy Publisher



Shahidi M¹ ; Abazari O¹ ; Dayati P² ; Bakhshi A¹ ; Zavarreza J¹ ; Modarresi MH³ ; Haghiralsadat F⁴ ; Rahmanian M⁵ ; Naghib SM⁶ ; Tofighi D⁷
Source: Frontiers in Bioengineering and Biotechnology Published:2022

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. Copyright © 2022 Shahidi, Abazari, Dayati, Bakhshi, Zavarreza, Modarresi, Haghiralsadat, Rahmanian, Naghib and Tofighi.