Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide

Lv, Yao; Tao, Lei; Bligh, S. W. Annie; Yang, Huihui; Pan, Qixia; Zhu, Li‐Min

doi:10.1016/j.msec.2015.10.065

Cited by 73 publications

(36 citation statements)

References 46 publications

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“…This finding suggests that DOX is scarcely released in cell culture media and that the GOfMLP uptake mechanism is favored by FPR receptor. These data agree with different studies using graphene oxide‐based platforms for DOX delivery in vitro, where it was observed a decrease of viability between 20 and 50% after exposure to drug concentrations around 20 × 10 −6 m for 24 h . Nevertheless, we would like to underline the differences regarding the physicochemical characteristics of the carriers, their specific functionalization targeting different ligands on cell membranes or the differences in drug sensitivity according to the cell line used in the different studies.…”

Section: Resultssupporting

confidence: 90%

A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

Martín

Ruiz

Keshavan

et al. 2019

Adv Funct Materials

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The design of multifunctional materials able to both selectively deliver a drug into cells in a targeted manner and display an enhanced propensity for biodegradation is an important goal. Here, graphene oxide (GO) is functionalized with the chemotactic peptide N-formyl-methionyl-leucylphenylalanine (fMLP) known to interact with the formyl peptide receptor, which is expressed in different cancer cells, including cervical carcinoma cells. This study highlights the ability of GOfMLP for targeted drug delivery and cancer cell killing and the subsequent degradation capacity of the hybrid. Biodegradation is assessed via Raman spectroscopy and transmission electron microscopy. The results show that GOfMLP is susceptible to faster myeloperoxidase-mediated degradation. The hybrid material, but not GO, is capable of inducing neutrophil degranulation with subsequent degradation, being the first study showing inducible neutrophil degradation by the nanomaterial itself with no prior activation of the cells. In addition, confocal imaging and flow cytometry using HeLa cells demonstrate that GOfMLP is able to deliver the chemotherapeutic agent doxorubicin faster into cells, inducing higher levels of apoptosis, when compared to nonfunctionalized GO. The results reveal that GOfMLP is a promising carrier able to efficiently deliver anticancer drugs, being endowed with the ability to induce its own biodegradation.

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Section: Resultssupporting

confidence: 90%

A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

Martín

Ruiz

Keshavan

et al. 2019

Adv Funct Materials

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“…The literature reports that when TGA is performed on the raw materials, at 900 °C CMC, FI, LA and Ac all exhibit 100% weight loss (Lv, et al, 2016;Wen, et al, 2013). The data obtained in this work are given in Fig.…”

Section: Go Go-cmc Go-cmc-fi-la-ac Go-cmc-fi-acmentioning

confidence: 61%

Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems

Pan

Williams

et al. 2016

Carbohydrate Polymers

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113

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In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems.

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“…On the other hand, at the very moment DOX was loaded, DOX loaded GO sheets showed more aggregation. But, the GO modified with PEG and lactobionic acid by EDC-NHS chemistry exhibited potency for DOX loading up to 85% [61]. Simultaneously, PEGylated green synthesised silver nanocomposites can load DOX up to 87% [7].…”

Section: Drug Entrapment Efficiency (%Ee) and Drug Loading Content (%mentioning

confidence: 99%

“…The acidic pH of the solution might trigger DOX release by weakening the hydrogen bonds between DOX and GO (-OH and -COOH), reducing the non-covalent interactions and hydrogen bonding. Furthermore, NGO-AgNPs-PEG-DOX was able to have higher and controlled DOX release than NGO-DOX, as the release of DOX from NGO-DOX was not so pH controlled as from the charge-reversal PEGylated GO [61]. Hence, as acidic environment favors higher and controlled DOX release from NGO-AgNPs-PEG-DOX, the micro-environments of cancerous tissues, which have low pH as well as the presence of intracellular lysosomes or endosomes, trigger drug release at the targeted cancerous tissues.…”

Section: Drug Release Responsementioning

confidence: 99%

Green synthesized amino-PEGylated silver decorated graphene nanoplatform as a tumor-targeted controlled drug delivery system

Palai

Mondal

Chakraborti³

et al. 2019

SN Appl. Sci.

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In this study design, the PEGylated silver decorated graphene nanocomposites (NGO-AgNPs-PEG) were successfully prepared by eco-friendly non-toxic green synthesis following a novel syn-graphenization method using the aqueous leaf extract of Azadirachta indica (A. indica) (neem) as reducing agent. The prepared Smart pH stimuli responded nanoplatform was thoroughly characterized by various analytical techniques. Since a functional nanocarrier is very essential for cancer therapy, it could quickly guide the loaded anticancer drug to the tumor site to decrease the side effect. In order to overcome the side effects of doxorubicin (DOX), an anticancer drug, it was incorporated into amino PEGylated NGO-AgNPs nanocomposites. Considering drug loading and release studies, it may be concluded that improved drug loading efficiency (218%) and more pH-responsive controlled release (following Korsmeyer-Peppas model release kinetics) of DOX from NGO-AgNPs-PEG lead to a promising nanocarrier for the anticancer drug. The cytotoxicity study results, on HaCaT cell lines, indicated DOX-loaded PEGylated functionalized nanographene oxides, as compared to free DOX, had lesser harmful effect on normal cells than cancer cells. Increased cytotoxicity was exhibited in the cancerous cells (HeLa cell lines) treated with DOX loaded PEGylated silver functionalized nanographene oxide compared to covalently conjugated NGO-DOX. So, the effective delivery and release of the anticancer drug into acidic microenvironment of the targeted tumour cells would bring out higher therapeutic efficacy than pure NGO. Such a gold standard biocompatible PEGylated silver decorated NGO theranostic nanoplatform may be an excellent nano cargo for targeted and controlled drug delivery in cancer therapy.

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Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide

Cited by 73 publications

References 46 publications

A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems

Green synthesized amino-PEGylated silver decorated graphene nanoplatform as a tumor-targeted controlled drug delivery system

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