Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer

Abstract

2020) Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer, Drug Delivery, 27:1, 15-25, ABSTRACT Small interfering RNA (siRNA) exhibits great potential as a novel therapeutic option due to its highly sequence-specific ability to silence genes. However, efficient and safe delivery carriers are required for developing novel therapeutic paradigms. Thus, the successful development of efficient delivery platforms for siRNA is a crucial issue for the development of siRNA-based drugs in cancer treatments. In this study, biocompatible selenium nanoparticles (SeNPs) were loaded with RGDfC peptide to fabricate tumor-targeting gene delivery vehicle RGDfC-SeNPs. Subsequently, RGDfC-SeNPs were loaded with Derlin1-siRNA to fabricate RGDfC-Se@siRNA, which are functionalized selenium nanoparticles. RGDfC-Se@siRNA showed greater uptake in HeLa cervical cancer cells in comparison with that in human umbilical vein endothelial cells (HUVECs), verifying the RGDfC-mediated specific uptake of RGDfC-Se@siRNA. RGDfC-Se@siRNA was capable of entering HeLa cells via clathrin-associated endocytosis, and showed faster siRNA release in a cancer cell microenvironment in comparison with a normal physiological environment. qPCR and western blotting assays both indicated that RGDfC-Se@siRNA exhibited an obvious gene silencing efficacy in HeLa cells. RGDfC-Se@siRNA suppressed the invasion, migration and the proliferation of HeLa cells, and triggered HeLa cell apoptosis. Moreover, RGDfC-Se@siRNA induced the disruption of mitochondrial membrane potentials. Meanwhile, RGDfC-Se@siRNA enhanced the generation of reactive oxygen species (ROS) in HeLa cell, suggesting that mitochondrial dysfunction mediated by ROS might play a significant role in RGDfC-Se@siRNA-induced apoptosis. Interestingly, RGDfC-SeNPs@siRNA exhibited significant antitumor activity in a HeLa tumor-bearing mouse model. Additionally, RGDfC-SeNPs@siRNA is nontoxic to main organ of mouse. The above results indicate that RGDfC-Se@siRNA provides a promising potential for cervical cancer therapy. ARTICLE HISTORY

Gambogic Acid as a Candidate for Cancer Therapy: A Review

“…Furthermore, multifunctional nanoparticles have been investigated for pH-sensitive, redoxsensitive, receptor targeting response, which may enhance drug release, improve drug accumulation in the tumor and reduce some side effects of GA. For example, hyaluronic acid (HA), folic acid (FA) and RGD are conjugated to the surfaces of the carriers for higher anticancer efficiency. 84,85 Micelles Self-assembled polymeric micelles have received growing attention in the field of drug delivery systems in recent years owing to the ability of drug solubilization, sustained drug release and drug targeting. 86 Polymeric micelles consist of amphiphilic block copolymers, having a hydrophilic shell and a hydrophobic core, which can be used as a promising drug delivery system for the hydrophobic drugs.…”

“…Furthermore, multifunctional nanoparticles have been investigated for pH-sensitive, redox-sensitive, receptor targeting response, which may enhance drug release, improve drug accumulation in the tumor and reduce some side effects of GA. For example, hyaluronic acid (HA), folic acid (FA) and RGD are conjugated to the surfaces of the carriers for higher anticancer efficiency. 84 , 85 …”

Recent Advances in Semiconducting Monoelemental Selenium Nanostructures for Device Applications

“…Fluorescent semiconductor Se nanomaterials have attracted considerable interest for a wide variety of promising applications because Se is a trace element, naturally found in the body, therefore holds more significance in bioimaging as compared to many other metal and metal oxide nanomaterials. [ 167–169 ] In addition, Se nanomaterials are capable of anticancer, [ 9,170,171 ] antimicrobial, [ 172 ] antioxidant, [ 28,173 ] anti‐inflammatory activities, [ 174 ] and thus they can potentially be simultaneously used as both diagnostic tools (cell labelling) and therapeutic agents in practical applications. Hassanien et al [ 175 ] gave the photoluminescence (PL) spectra of Se nanoparticles synthesized by Moringa oleifera leaf extract technique.…”

<p>Silencing of MEF2D by siRNA Loaded Selenium Nanoparticles for Ovarian Cancer Therapy</p>

“…This finding was consistent with previous publications. 13,29 Apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA was assessed using flow cytometry. From Figure 6C, a sub-G1 apoptosis peak in the R-Se@MEF2D-siRNA group was more obvious (20.15%) compared to the R-Se@siNC group (6.42%) or untreated control group (6.19%), proving that R-Se@MEF2D-siRNA obviously induced the apoptosis of SKOV3 cells.…”