Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells
BIOMEDICINE & PHARMACOTHERAPY
Authors: Alinejad, Vahideh; Somi, Mohammad Hossein; Baradaran, Behzad; Akbarzadeh, Parvin; Atyabi, Fatemeh; Kazerooni, Hanif; Kafil, Hosein Samadi; Maleki, Leili Aghebati; Mansouri, Homayoon Siah; Yousefi, Mehdi
Abstract
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-kappa B 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 114 nm size; with polydispersity index and zeta potential about 0.3 and 10.1 mV 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-kB 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. (C) 2016 Elsevier Masson SAS. All rights reserved.
Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration
ANNALS OF THE RHEUMATIC DISEASES
Authors: Reddi, AH
Abstract
Background: Articular cartilage homoeostasis is critical for joint function. The steady state homoeostasis of articular cartilage is a balance between anabolic morphogens such as cartilage derived morphogenetic proteins (CDMPs) and bone morphogenetic proteins (BMPs) of the BMP family and catabolic cytokines such as interleukin (IL)1, IL17, and tumour necrosis factor alpha. Although bone and articular cartilage are adjacent tissues, there is a profound difference in their regeneration potential. Bone has the highest potential for regeneration. On the other hand, articular cartilage is recalcitrant to repair. Objective: To examine the hypothesis that the feeble innate regeneration ability of cartilage is due to the preponderance of catabolic cytokines such as IL1 and IL17. Results: During a systematic investigation of CDMPs and cytokines IL17B (chondroleukin) was found in bovine articular cartilage. Discussion and conclusions: BMP-7 and IL17B are present in articular cartilage and synthesised in chondrocytes as shown by northern blots and real-time reverse transcription-polymerase chain reaction. The coexistence of anabolic morphogens and catabolic cytokines in articular cartilage has important implications for cartilage homoeostasis and regeneration. The networks of signalling systems of morphogens and cytokines determine the net capacity for regenerative morphogenesis of articular cartilage. Finally, the feeble innate capacity for articular cartilage may be improved by targeted therapy by soluble receptors to block catabolic cytokines.