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Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.

ABSTRACT: Nano-graphene oxide (NGO) has been proposed as a novel drug carrier. However, the poor biocompatibility and physiological stability as well as lack of cancer targeting capability have limited its further applications in cancer therapy. To solve this problem, we developed a novel nanohybrid of NGO/DOX@SPC-FA by first allowing soy phosphatidylcholine membrane (SPC) to encapsulate DOX-loaded NGO (NGO/DOX) and then modifying the SPC membrane with PEGylated lipid-FA conjugate to achieve the display of cancer targeting FA on the nanohybrid surface. The SPC membrane (mimicking cell membrane) enabled the resultant nanohybrids (NGO/DOX@SPC-FA) to exhibit good stability and biocompatibility, high drug loading capability, efficient cellular uptake, and controlled drug release. Moreover, compared with NGO/DOX and SPC-modified NGO/DOX (NGO/DOX@SPC), the FA-modified NGO/DOX@SPC nanohybrids (NGO/DOX@SPC-FA) could deliver NGO/DOX to cancer cells with improved delivery and killing efficacy due to the presence of FA targeting motifs on the surface. The NGO/DOX@SPC-FA nanohybrids were found to be internalized specifically by FA-positive cancer cells (Hela cells) through both macropinocytosis-directed engulfment and clathrin-dependent endocytosis, and then become localized into the lysosomes. In vivo biodistribution study showed that NGO/DOX@SPC-FA had a high tumor targeting ability because of the active targeting mechanism with folate modification. In vivo antitumor therapy study demonstrated NGO/DOX@SPC-FA could significantly inhibit tumour growth and prolong the survival time of mice. Our results suggest that NGO/DOX@SPC-FA, as a novel drug delivery system with high drug loading and targeted delivery efficiency, holds promise for future cancer therapy.

SUBMITTER: Ma K

PROVIDER: S-EPMC6147173 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.

Ma Kun K Fu Duo D Liu Yajun Y Rui Dai Yu Dongli D Guo Zhaoming Z Cui Changhao C Wang Li L Xu Jinaqiang J Mao Chuanbin C

Journal of materials chemistry. B 20180725 31

Nano-graphene oxide (NGO) has been proposed as a novel drug carrier. However, the poor biocompatibility and physiological stability as well as lack of cancer targeting capability have limited its further applications in cancer therapy. To solve this problem, we developed a novel nanohybrid of NGO/DOX@SPC-FA by first allowing soy phosphatidylcholine membrane (SPC) to encapsulate DOX-loaded NGO (NGO/DOX) and then modifying the SPC membrane with PEGylated lipid-FA conjugate to achieve the display o ...[more]

PMID: 30245822

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Project description:Purpose:The antitumoral effect of ATP requires its accumulation in the extracellular space to interact with membrane receptors in target cells. We propose the use of albumin nanoparticles (ANPs) coated with erythrocyte membranes (EMs) to load, deliver, release, and enhance the extracellular anticancer activity of ATP. Materials and methods:ANPs were synthesized by desolvation method and optimal values of pH, albumin concentration, and ethanol volume were determined. EMs were derived from erythrocyte lysates and were coated on to ANPs using an extruder. Size was determined by transmission electron microscopy (TEM) and hydrodynamic size and zeta potential were determined by dynamic light scattering. Coating of the ANPs with the EMs was verified by TEM and confocal microscopy. Nanoparticle cell uptake was analyzed by confocal microscopy using HeLa and HEK-293 cell cultures treated with nanoparticles stained with 1,1'-diocta-decyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (DiD) for EM-ANPs and Alexa 488 for ANPs. Cell viability was analyzed by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and Annexin V/propidium iodide assays. Results:Optimal values of ANP preparation were as follows: pH=9, 10 mg/mL albumin concentration, and 2.33±0.04 mL ethanol volume. Size distributions as analyzed by TEM were as follows: ANPs =91.9±4.3 nm and EM-ANPs =98.3±5.1 nm; hydrodynamic sizes: ANPs =180.5±6.8 nm and EM-ANPs =197.8±3.2 nm; and zeta potentials: ANPs =17.8±3.5 mV, ANPs+ATP =-13.60±0.48 and EM-ANPs =-13.7±2.9 mV. The EMs coating the ANPs were observed by TEM and confocal microscopy. A fewer number of internalized EM-ANPs+ATP compared to non-coated ANPs+ATP was observed in HeLa and HEK-293 cells. Cell viability decreased up to 48.6%±2.0% with a concentration of 400 µM ATP after 72 hours of treatment and cell death is caused mainly via apoptosis. Conclusion:Our current results show that it is possible to obtain nanoparticles from highly biocompatible, biodegradable materials and that their coating with EMs allows the regulation of the internalization process in order to promote extracellular activity of ATP.

Dataset Information

Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.

Publications

Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.

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