Preparation of graphene oxide/dendrimer hybrid carriers for delivery of doxorubicin

Siriviriyanun, Ampornphan; Popova, Marina; Imae, Toyoko; Kiew, Lik Voon; Looi, Chung Yeng; Wong, Won Fen; Lee, Hong Boon; Chung, Lip Yong

doi:10.1016/j.cej.2015.07.024

Cited by 38 publications

(17 citation statements)

References 39 publications

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“…The amount of DOX entrapped in the polymeric nanocarriers was determined from the absorbance of a 232 nm band based on a calibration curve with known concentrations of DOX up to 150 μg mL −1 in water in accordance with the procedure previously reported . The determined amount of unbound DOX in the dialyzed outer solution was subtracted from the initial amount of DOX to calculate the amount of loaded DOX.…”

Section: Methodsmentioning

confidence: 99%

A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

Viswanathan

Hsu

Voon

et al. 2016

Macromolecular Bioscience

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Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.

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Section: Methodsmentioning

confidence: 99%

A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

Viswanathan

Hsu

Voon

et al. 2016

Macromolecular Bioscience

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“…Graphene based nanomaterials possess large specific surface areas (theoretical value ~ 2630 m 2 g -1 ) [2,10] and are able to complex with aromatic drugs via π-π stacking and/or hydrophobic interaction [11,12] for excellent drug storage property [13] . Moreover, drugs loaded on graphene are highly stable to avoid any premature release outside the target cell.…”

Section: Introductionmentioning

confidence: 99%

Highly efficient nuclear delivery of anti-cancer drugs using a bio-functionalized reduced graphene oxide

Zheng

Xiao

2016

Journal of Colloid and Interface Science

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Targeted drug delivery has become important, attractive and challenging in biomedical science and applications. Anti-HER2 antibody-conjugated poly-l-lysine functionalized reduced graphene oxide (anti-HER2-rGO-PLL) nanocarriers were prepared to efficiently deliver doxorubicin targeting at the nucleus of HER2 over-expressing cancer cells. The polycationic PLL was first covalently grafted to graphene oxide (GO) nanosheets followed by reduction to obtain rGO-PLL with high drug loading and good colloidal stability. The anti-HER2 antibodies were subsequently conjugated to the amino groups of PLL to achieve excellent cell uptake capability. Cellular uptake of anti-HER2-rGO-PLL into MCF7/HER2 cells is significantly higher than that of rGO-PLL due to the specific targeting of anti-HER2 to HER2 overexpressing breast cancer cells. Additionally the anti-HER2-rGO-PLL enables a fast accumulation of DOX inside the nucleus, its subcellular site of action. In vitro cytotoxicity measurements clearly reveal a seven fold improvement in the anticancer efficacy for anti-HER2-rGO-PLL/DOX in comparison to rGO-PLL/DOX. The enhanced anticancer efficacy could be ascribed to the different intracellular DOX distributions resulted from the different internalization routes that are energy-dependent macropinocytosis and energy-independent direct penetration by anti-HER2-rGO-PLL and rGO-PLL, respectively. The results demonstrate that anti-HER2 conjugated rGO-PLL developed is a promising vehicle for efficient nuclear delivery of chemotherapeutic agents to HER2 over-expressing tumours.

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“…Nevertheless, the passive targeted efficiency of the EPR effect is insufficient to achieve a high enough concentration of drug in malignant tumor tissues. To conquer this limitation, targeting ligands that can distinguish cancer cells from normal ones and stimulate receptor‐mediated endocytosis, have been implemented in several drug delivery systems …”

Section: Introductionmentioning

confidence: 99%

“…[12,13] Nevertheless, the passivetargeted efficiency of the EPR effect is insufficient to achieve ah igh enough concentration of drugi nm alignant tumor tissues.T o conquer this limitation, targeting ligandst hat can distinguish cancer cells from normal ones and stimulate receptor-mediated endocytosis, have been implemented in severald rug delivery systems. [14][15][16][17] The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer-drug conjugate methoxy poly(ethylene glycol)poly(g-benzyl l-glutamate)-disulfide-docetaxel (PEG-PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)folic acid (PEG-FA), for enhanced targets pecificity and improveda nticancere fficiency of docetaxel (DTX). The spherical PEG-PBLG-SS-DTX/PEG-FAm ixed micelles prepared by the dialysis methodr evealed an arrowly distributed size at 129.7 AE 2.1 nm with low polydispersity of 0.10 AE 0.02.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

Zhang

et al. 2016

ChemPlusChem

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The objective of this study was to build mixed micelles based on two functional co‐polymers, including the redox‐sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ‐benzyl l‐glutamate)‐disulfide‐docetaxel (PEG–PBLG‐SS‐DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG‐SS‐DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL−1, indicating excellent self‐assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl‐dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining, respectively, on folate receptor (FR)‐negative A549 and FR‐positive MCF‐7 cells. The mixed micelles could be taken up efficiently by MCF‐7 cells by FR‐mediated endocytosis compared with PEG–PBLG‐SS‐DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF‐7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox‐sensitive PEG–PBLG‐SS‐DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.

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Preparation of graphene oxide/dendrimer hybrid carriers for delivery of doxorubicin

Cited by 38 publications

References 39 publications

A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

Highly efficient nuclear delivery of anti-cancer drugs using a bio-functionalized reduced graphene oxide

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

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