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Autoimmune diseases (AD), which are classified as chronic injuries, are caused by a specific auto-reactive reaction. The etiology of most ADs is not well understood. Meanwhile, Autophagy is a protective response defining as a catabolic method by lysosomes tending to maintain homeostasis acts by recycling and discrediting cell compartments. Autophagy plays a crucial role in controlling immune homeostasis by eliminating intracellular pathogens and presenting antigens to immune cognition. MicroRNAs are commonly known as endogenous non-coding small RNAs, which span 18–25 nt and take part in the gene expression at the post-transcriptional level regulation. miRNAs play important roles in different processes like, cell differentiation, duplicating, and apoptosis. Moreover, miRNAs are the critical molecules for the regular function of the immune system by modulating immune tolerance mechanisms and autoimmunity. Recent findings support the role of dysregulated miRNAs in the pathogenesis of ADs and in the regulation of autophagy. In this review, we will focus on the role of the miRNAs in the regulation of autophagy and then will explain the role of dysregulated miRNAs in the initiation of the ADs by modulating autophagy. [ABSTRACT FROM AUTHOR]

• A novel biodegradable micelle was synthesized with small size and low CMC value. • Doxorubicin and curcumin loaded micelle induced apoptosis. • Dual drug loaded micelle showed a synergistic effect. • Dual drug loaded micelle showed intrinsic apoptosis pathways in the genetic and protein levels. This study aimed to design an effective targeted combination of doxorubicin (Dox)-Curcumin (Cur) delivery system to eradicate the MDA-MB231 cell line. A novel biodegradable poly ε-Caprolactone-co-maleic anhydride-graft-citric acid copolymer micelle (PCL-co-P(MA-g-CA)) was synthesized through thiolen radical copolymerization and ring-opening polymerization. The unique micelle structure allowed simultaneous loading of hydrophilic Dox and hydrophobic Cur with a loading efficiency of above 98 % for each drug. The physicochemical characterization of copolymeric micelle was analyzed by 1HNMR, 13CNMR, FTIR, DSC, CMC, DLS and SEM. The in vitro cytotoxicity was assessed by MTT assay, cell cycle analysis, annexin V-FITC apoptosis, qRT-PCR and western blot. The final obtained micelles with critical micelle concentration (CMC) of 0.5 μg/mL, and particle size and surface charge was 60 nm and -14.1 mV, respectively. Beside the fast uptake of designed micelle, Dox@Cur loaded micelle showed a synergistic effect with the combination index (CI) value of below 1. Our results revealed that this novel engineered combinatorial micelle induced apoptosis (96 %) which was proved by annexin V and cell cycle. qRT-PCR and western blot assays demonstrated involvement of intrinsic apoptosis pathways in the genetic and protein levels. Finally, the penetration of Dox@Cur loaded micelle was evaluated by 3D in vitro tumor formation. Our findings showed the penetration behavior of micelles is in a concentration-dependent manner. In conclusion, combinational therapy by using Dox and Cur nano-formulation has boosted the cytotoxicity in MDA-MB231 cells by promoting the apoptotic response. [ABSTRACT FROM AUTHOR]

• A PAMAM dendrimer encapsulated curcumin and a polyplex with siRNA against BCL2. • Characterization, drug release and photostability was investigated. • Uptake by HeLa cells studied by fluorescence microscopy and FACS analysis. • The nanoformulation showed higher cytotoxicity than PAMAM-Cur and free Cur. • Apoptosis was studied by annexin-V and DAPI staining. Co-delivery of therapeutic agents and small interfering RNA (siRNA) can be achieved by a suitable nanovehicle. In this work, the solubility and bioavailability of curcumin (Cur) were enhanced by entrapment in a polyamidoamine (PAMAM) dendrimer, and a polyplex was formed by grafting Bcl-2 siRNA onto the surface amine groups to produce PAMAM-Cur/Bcl-2 siRNA nanoparticles (NPs). The synthesized polyplex NPs had a particle size of ∼180 nm, and high Cur loading content of ∼82 wt%. Moreover, the PAMAM-Cur/Bcl-2 siRNA NPs showed more effective cellular uptake, and higher inhibition of tumor cell proliferation compared to PAMAM-Cur nanoformulation and free Cur, due to the combined effect of co-delivery of Cur and Bcl-2 siRNA. The newly described PAMAM-Cur/Bcl-2 siRNA polyplex NPs could be a promising co-delivery nanovehicle. [ABSTRACT FROM AUTHOR]