Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer.

Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.

siRNAs are small biomolecules shown as novel insights in cancer gene therapy because of their capability to silence target genes. However, achieving an effective biocompatible system for siRNA delivery to the tumor site remains a significant challenge. This work aimed to develop a nanoparticle-based delivery system consisting of selenium nanoparticles modified by chitosan and hyaluronic acid to sustain the release of siRNAs to bladder cancer cells. The results of this study demonstrated that this nanosystem successfully silenced the PLK1 gene and reduced the proliferation in vitro and in vivo. These findings suggest that hyaluronic acid-chitosan-selenium nanoparticles may open a new insight for targeted gene therapy for bladder cancer.

Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes.

Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo, the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells.

Silymarin reduces retinal microvascular damage in streptozotocin-induced diabetic rats.

Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ + silymarin (50 mg/kg), and STZ + silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-κB p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.

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

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.

MXene-based cytosensor for the detection of HER2-positive cancer cells using CoFe2O4@Ag magnetic nanohybrids conjugated to the HB5 aptamer.

MXenes are a new class of conductive two-dimensional material which have received growing attention in biosensing for their significant surface area and unique surface chemistry. Here, gold electrodes were modified with MXene nanosheets of about 2 nm thickness and 1.5 µm lateral size for the electrochemical detection of tumor cells. An HB5 aptamer with high selectivity for HER-2 positive cells was immobilized on the MXene layers via electrostatic interactions. To minimize electrode biofouling with blood matrix, magnetic separation of HER-2 positive circulating tumor cells was carried out using CoFe2O4@Ag magnetic nanohybrids bonded to the HB5. The formation of sandwich-like structures between the magnetically captured cells and the functionalized MXene electrodes effectively shields the electron transfer of a redox probe, enabling quantitative cell detection using the change in current. This label-free MXene-based cytosensor platform yielded a wide linear range of 102-106 cells/mL, low detection limit of 47 cells/mL, and good sensitivity and selectivity in the detection of HER2-posetive cells in blood samples. The presented aptacytosensor demonstrates the great potential of using CoFe2O4@Ag magnetic nanohybrids and MXenes to monitor cancer progression via circulating tumor cells in blood at low cost.