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:10.3389/fbioe.2022.949704

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

Front Bioeng Biotechnol. 2022 Aug 5:10:949704. doi: 10.3389/fbioe.2022.949704. eCollection 2022.

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
² Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
³ Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
⁵ Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
⁶ Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology (IUST), Tehran, Iran.
⁷ Department of Psychology, Epidemiology, and Research Design Support (BERD), Clinical and Translational Science Center, University of NM, Albuquerque, NM, United States.

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.

Keywords: PD-L1; PLGA-PEG; bladder cancer; mesoporous silica nanoparticles; miR-34a.