PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells

Abstract

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.

Medicated Nanoparticle for Gene Delivery

“…In the nonviral gene delivery overcoming biological barriers in the circulation or inside the target cell and transferring the gene vector is based on the molecular weight of the vector, ratio between the vector nitrogens and the DNA phosphates (termed the N:P ratio) and the salt concentration of the buffer solution. [27][28][29][30].…”

Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology

“…However, the disadvantages of PEI-or cationic liposome-based gene carriers are the cytotoxicity induced by excess positive charge as well as the aggregation on the cell surface. To overcome those detriments, biodegradable PLGA nanospheres may be very helpful particularly for efficient delivery of cytosolic therapeutics such as miRNAs (Vasir and Labhasetwar, 2007;Liang et al, 2011).…”

Tumor Imaging and Interferon-γ–Inducible Protein-10 Gene Transfer Using a Highly Efficient Transferrin-Conjugated Liposome System in Mice

“…Liposomes containing different lipid compounds or spacer units display varying levels of cytotoxicity (23,32). For example, poly (D,L-lactide-co-glycolide) (PLGA)-based nanoparticles and commercial Lipo2000 show about 90% and 86% cell viability, respectively (32).…”