Drug delivery systems for cancer chemotherapy are employed to improve the effectiveness and decrease the side-effects of highly toxic drugs. Most chemotherapy agents have indiscriminate cytotoxicity that affects normal, as well as cancer cells. To overcome these problems, new more efficient nanosystems for drug delivery are increasingly being investigated. Polyamidoamine (PAMAM) dendrimers are an example of a versatile and reproducible type of nanocarrier that can be loaded with drugs, and modified by attaching target-specific ligands that recognize receptors that are over-expressed on cancer cells. PAMAM dendrimers with a high density of cationic charges display electrostatic interactions with nucleic acids (DNA, siRNA, miRNA, etc.), creating dendriplexes that can preserve the nucleic acids from degradation. Dendrimers are prepared by conducting several successive “generations” of synthetic reactions so their size can be easily controlled and they have good uniformity. Dendrimers are particularly well-suited to co-delivery applications (simultaneous delivery of drugs and/or genes). In the current review, we discuss dendrimer-based targeted delivery of drugs/genes and co-delivery systems mainly for cancer therapy.

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The results of this research has brough a new aspect concerning the proteevtive and positive effects of thymol on the diabetic complications in the animal model.

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The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the folate receptor expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer.