The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.
Objectives: miR-181a is involved in immunity, metabolism, tumor suppression or carcinogenesis reported by many other studies. However, its role in the development of chemosensitivity to adriamycin in low-invasive breast cancer cells remains unclear. The aim of this study is to define the function role of miR-181a in promoting the efficacy of adriamycin-based neoadjuvant chemotherapy. Methods: Cell survival analysis was detected by Cell Counting Kit-8 assay. Apoptotic cells were quantitatively detected using FITC Annexin V apoptosis Detection Kit I. Bcl-2 protein expression was measured by western blot. Luciferase reporter vector with the putative BCL-2 3' untranslated region (3'UTR) was constructed to explore whether BCL-2 was a direct target gene of miR-181a. Real-time PCR was performed to test the expression of miR-181a and Bcl-2 in the selected breast cancer tissue samples. Results: The down-regulation of miR-181a decreased adriamycin-induced apoptosis in MCF-7 cells. Transfected with miR-181a mimic in cells resulted in the decreased expression of Bcl-2. The alteration of miR-181a expression did not significantly affect the chemosensitivity to adriamycin in MCF-7 and MCF-7/ADR cells with genetic knockout of Bcl-2. miR-181a may suppress Bcl-2 expression by forming imperfect base pairing with the 3'UTR of Bcl-2 gene such that a negative relationship between miR-181a and Bcl-2 in MCF-7 and MCF-7/ADR cells is observed. Conclusions: At least in part, the detection of miR-181a may direct the clinical medication in patients with neoadjuvant chemotherapy because of miR-181a enhanced adriamycin-induced apoptosis via targeting Bcl-2.
Prospects for future growth and development in this field are quite good in Asia as rapid healthcare inflation, increasing rates of chronic conditions and aging population, and increasing technology diffusion will underpin the need for greater awareness of the need to incorporate economic efficiency into the health-care systems.
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