Chitosan (CMD)-mediated co-delivery of SN38 and Snail-specific siRNA as a useful anticancer approach against prostate cancer.

BACKGROUND: Prostate cancer is known as the most common malignancy in men. Chitosan has generated great interest as a useful biopolymer for the encapsulation of small interfering RNA (siRNA). Due to cationic nature, chitosan is able to efficiently encapsulate siRNA molecules and form nanoparticles. Furthermore, the biocompatible and biodegradable attributes of chitosan have paved the way for its potential application in the in vivo delivery of therapeutic siRNAs. In this study, we aimed to design chitosan/CMD nanoparticles for the efficient encapsulation of the anti-cancer drugs SN38 and Snail-specific siRNA. METHODS: Physicochemical characteristics, growth inhibitory properties, and anti-migratory capacities of the dual delivery of SN38-Snail siRNA CMD-chitosan nanoparticles were investigated in prostate cancer cells. RESULTS: Our findings provided evidence for the suggestion that, ChNP-CMD-SN38-siRNA treated cells, the mRNA level of snail decreased from 1.00 to 0.30 (±0.14) and 0.09 (±0.04) after 24h and 48h, respectively. Additionally, the fold induction of E-cadherin and Claudin-1 increased from 1.00 to now 3.12 (±0.62), 3.02 (±0.28) after 24h and 5.6 (±0.91), 4.42 (±0.51) after 48h, respectively. Also, co-delivery of SN38 and Snail-specific siRNA by an appropriate nanocerrier (chitosan nanoparticles) could reduce the viability, proliferation, and migration of PC-3 cells. CONCLUSIONS: In conclusion, ChNPs encapsulating SN38 and Snail-specific siRNA may represent huge potential as an effective anti-cancer drug delivery system for the treatment of prostate cancer.

Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells.

Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients.IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF-κB as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114nm size; with polydispersity index and zeta potential about 0.3 and 10.1mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA-MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-κB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer.

Effect of Superparamagnetic Iron Oxide Nanoparticles-Labeling on Mouse Embryonic Stem Cells.

OBJECTIVE: Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label mammalian cells and to monitor their fate in vivo using magnetic resonance imaging (MRI). However, the effectiveness of phenotype of labeled cells by SPIONs is still a matter of question. The aim of this study was to investigate the efficiency and biological effects of labeled mouse embryonic stem cells (mESCs) using ferumoxide- protamine sulfate complex. MATERIALS AND METHODS: In an experimental study, undifferentiated mESCs, C571 line, a generous gift of Stem Cell Technology Company, were cultured on gelatin-coated flasks. The proliferation and viability of SPION-labeled cells were compared with control. ESCs and embryoid bodies (EBs) derived from differentiated hematopoietic stem cells (HSCs) were analyzed for stage-specific cell surface markers using fluorescence-activated cell sorting (FACS). RESULTS: Our observations showed that SPIONs have no effect on the self-renewal ability of mESCs. Reverse microscopic observations and prussian blue staining revealed 100% of cells were labeled with iron particles. SPION-labeled mESCs did not significantly alter cell viability and proliferation activity. Furthermore, labeling did not alter expression of representative surface phenotypic markers such as stage-specific embryonic antigen 1 (SSEA1) and cluster of differentiation 117 (CD117) on undifferentiated ESC and CD34, CD38 on HSCs, as measured by flowcytometry. CONCLUSION: According to the results of the present study, SPIONs-labeling method as MRI agents in mESCs has no negative effects on growth, morphology, viability, proliferation and differentiation that can be monitored in vivo, noninvasively. Noninvasive cell tracking methods are considered as new perspectives in cell therapy for clinical use and as an easy method for evaluating the placement of stem cells after transplantation.