Wang, Y, Gao, S, Ye, WH, Yoon, HS and Yang, YY. Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer. Nat Mater 5: 791-796

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
Nature Material (Impact Factor: 36.5). 11/2006; 5(10):791-6. DOI: 10.1038/nmat1737
Source: PubMed

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.

52 Reads
  • Source
    • "Recently, although some anticancer formulations (e.g. micellar nanoparticles, liposomes) have been successful in releasing more than one therapeutic agent, such as small molecule drugs, siRNA, plasmid DNA or peptide [12] [13] [14] [15] [16], sustained co-delivery of these agents remains inadequate due to Fig. 2. CLSM images of double-layered PLGA/PLLA microparticles. (a) A composite z-stack comprising five confocal sections was obtained for DOX (red) with a z-interval of 5.5 lm between images measured below and above the center plane of the DOX-loaded microparticles. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Double-layered microparticles composed of poly(D,L-lactic-co-glycolic acid, 50:50) (PLGA) and poly(L-lactic acid) (PLLA) were loaded with doxorubicin HCl (DOX) and paclitaxel (PCTX) through a solvent evaporation technique. DOX was localized in the PLGA shell, while PCTX was localized in the PLLA core. The aim of this study was to investigate how altering layer thickness of dual-drug, double-layered microparticles can influence drug release kinetics and their antitumor capabilities, and against single-drug microparticles. PCTX-loaded double-layered microparticles with denser shells retarded the initial release of PCTX, as compared with dual-drug-loaded microparticles. The DOX release from both DOX-loaded and dual-drug-loaded microparticles were observed to be similar with an initial burst. Through specific tailoring of layer thicknesses, a suppressed initial burst of DOX and a sustained co-delivery of two drugs can be achieved over 2 months. Viability studies using spheroids of MCF-7 cells showed that controlled co-delivery of PCTX and DOX from dual-drug-loaded double-layered microparticles were better in reducing spheroid growth rate. This study provides mechanistic insights into how by tuning the layer thickness of double-layered microparticles the release kinetics of two drugs can be controlled, and how co-delivery can potentially achieve better anticancer effects. Copyright © 2015. Published by Elsevier Ltd.
    Acta Biomaterialia 09/2015; DOI:10.1016/j.actbio.2015.08.051 · 6.03 Impact Factor
  • Source
    • "The hydrophilic shell, which is mainly composed of anionic, neutral, or cationic hydrophilic segments of amphiphilic polymer , takes the responsibility for keeping the stability of NPs. The NPs could deliver DNA (Qiu and Bae 2007; Wang et al. 2006), siRNA (Xiong et al. 2009; Zhu et al. 2010), or protein (Lee et al. 2009) with hydrophobic drugs simultaneously when the hydrophilic shell was composed of cationic hydrophilic polymeric segments. The polymeric matrix of carrier could be of synthetic or natural origin. "
    [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 · 2.18 Impact Factor
  • Source
    • "The application of nanotechnology to drug delivery accounts for the main part of nanomedicine.2,3 For example, nanotechnology can improve the solubility of hydrophobic drug to overcome the problem of system administration4,5 and can selectively deliver drugs to target tissues or cells,6 etc. Biodegradable polymeric nanoparticles have been high-lighted as drug delivery systems.7–10 Nanoparticulate systems, self-assembled from amphiphilic block copolymers, provide a unique core-shell architecture, in which the hydrophobic core can serve as a natural carrier environment for hydrophobic drugs while the hydrophilic shell allows particle stabilization in aqueous solution.11–13 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(å-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(å-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ≈25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.
    International Journal of Nanomedicine 03/2013; 8:971-982. DOI:10.2147/IJN.S39532 · 4.38 Impact Factor
Show more