Co-delivery of drugs and DNA from cationic core–shell nanoparticles self-assembled from a biodegradable copolymer

Abstract

Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications. Co-delivery of drugs and DNA has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies. Attempts have been made to deliver drugs and DNA simultaneously using liposomes. Here we report cationic core-shell nanoparticles that were self-assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer advantages over liposomes, as they are easier to fabricate, and are more readily subject to modulation of their size and degree of positive charge. More importantly, they achieve high gene-transfection efficiency and the possibility of co-delivering drugs and genes to the same cells. Enhanced gene transfection with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular, the co-delivery of paclitaxel with an interleukin-12-encoded plasmid using these nanoparticles suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast cancer cells.

PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells

“…Hence, a nanovector provides a platform for the integration of anticancer drugs and agents to decrease chemoresistance and then enhance treatment efficacy. 10,11 NPs with a smaller mean diameter have a lower loading efficacy and faster paclitaxel release due to shorter diffusion paths and larger surface areas. 24,25 The loading efficacy of Abbreviations: PLGA-PEI-TAX, poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles loaded with paclitaxel; PLGA-PEI-Cy5-S3SI, poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles loaded with cyanine-5-labeled signal transducer and activator of transcription-3 small interfering ribonucleic acid; PLGA-PEI-TAXCy5-S3SI, poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles loaded with paclitaxel and cyanine-5-labeled signal transducer and activator of transcription-3 small interfering ribonucleic acid; SD, standard deviation; siRNA, small interfering ribonucleic acid; TAX, paclitaxel.…”

“…10,11 The United States Food and Drug Administration approved the polymer poly(lactic-co-glycolic acid) (PLGA) for human use. The final product of PLGA using cellular metabolic conversion is water and carbon dioxide in a tricarboxylic acid cycle, and thus is recognized to be nontoxic.…”

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

“…[6][7][8][9] Some co-delivery nanoparticles (NPs) have been established to load two small-molecule anticancer drugs, for example, pirarubicin and paclitaxel, 10 doxorubicin (DOX) and paclitaxel, 11 or cisplatin and rapamycin, 12 or a small-molecule drug plus a macromolecule anticancer drug, such as, protein, 13 miRNA, 14 DNA, 15 or gene agents. 5 Co-NDDS synergistically inhibited the growth of the tumor compared with free drugs.…”

Nanoparticles Mediated Drug Delivery

“…It is mostly composed of polyamidoamines [15,16]. For example telodendrimers made of polyethylene glycol and dendritic cholic acid subunits [17,18].…”