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.
- SourceAvailable from: Xincheng Lu[Show abstract] [Hide abstract]
ABSTRACT: A series of amphiphilic N-(2-hydroxy)-propyl-3-trimethylammonium-chitosan-cholic acid (HPTA-CHI-CA) polymers were synthesized by grafting cholic acid (CA) and glycidyltrimethylammonium chloride onto chitosan. The self-assembly behavior of HPTA-CHI-CA was studied by fluorescence technique. The polymers were able to selfassemble into NPs in phosphate buffered saline with a critical aggregation concentration (CAC) in the range of 66-26 mg/L and the CAC decreased with the increasing of the degree of substitution (DS) of CA. The size of cationic HPTA-CHI-CA NPs ranges from 170 to 220 nm (PDI < 0.2). It was found that doxorubicin (DOX) could be encapsulated into HPTA-CHI-CA NPs based on self-assembly. The drug loading content and efficiency varies depending on the DS of CA and feeding ratio of DOX to polymer. In vitro release studies suggested that DOX released slowly from HPTA-CHI-CA NPs without any burst initial release. Besides, the confocal microscopic measurements indicated that DOX-HPTA-CHI-CA NPs could easily be uptaken by breast cancer (MCF-7) cells and release DOX in cytoplasm. Anti-tumor efficacy results showed that DOX-HPTA-CHI-CA NPs have a significant activity of inhibition MCF-7 cells growth. These results suggest cationic HPTA-CHI-CA may have great potential for anticancer drug delivery.Journal of Nanoparticle Research 12/2013; 15(12). DOI:10.1007/s11051-013-2123-2
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ABSTRACT: Clinical applications of siRNA are being hindered by poor intracellular uptake and enzymatic degradation. To address these problems, we devised an oral delivery system for telomerase reverse transcriptase siRNA using N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles (HNP). Both the porous structure and the positive charge of HNP facilitated siRNA encapsulation. The outer coating of HTCC not only protected siRNA from enzymatic degradation, but also improved siRNA permeability in intestine tract. In vivo and in vitro experiments proved that HNP could effectively deliver siRNA to lesion site and further into tumor cells. On the basis of confirming the antitumor activity of HNP:siRNA, we continued to encapsulate a hydrophobic chemotherapeutic drug-paclitaxel (PTX) into HNP to form a "two-in-one" nano-complex (HNP:siRNA/PTX). We demonstrated that HNP:siRNA/PTX could simultaneously ferry siRNA and PTX into tumor cells and increase drug concentration, which, in particular, was much more effective in tumor suppression than that of traditional cocktail therapy. These results suggested that the HNP, as a powerful delivery system for both siRNA and chemotherapeutic drug, would have a far-reaching application in human cancer therapy.Biomaterials 02/2013; 34(15). DOI:10.1016/j.biomaterials.2013.02.030
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ABSTRACT: In this study, a new type of folate-decorated thermoresponsive micelles based on the star- shaped amphiphilic block copolymer 4s [poly (ɛ-caprolactone)-b-2s (poly (N- isopropylacrylamide-co-acrylamide)-b′-methoxy poly (ethylene glycol)/poly (ethylene glycol)-folate)](ie, 4s [PCL-b-2s (P (NIPAAm-co-AAm)-b′-MPEG/PEG-FA)](PCIAE-FA)), were developed for the tumor-targeted delivery and temperature-induced controlled release of hydrophobic anticancer drugs. These amphiphilic star copolymers are capable of self- ...International Journal of Pharmaceutics 11/2012; 437(1):70-79.