Pluronic F127 self-assembled MoS2 nanocomposites as an effective glutathione responsive anticancer drug delivery system.

Adhisankar Vadivelmurugan,Rajeshkumar Anbazhagan,Vinothini Arunagiri,Juin-Yih Lai,Hsieh-Chih Tsai

doi:10.1039/c9ra04249k

Adhisankar Vadivelmurugan, Rajeshkumar Anbazhagan + Show 3 more

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https://doi.org/10.1039/c9ra04249k

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Abstract

In this study, bio-responsive polymeric MoS2 nanocomposites were prepared for use as a drug carrier for cancer therapy. Herein, we report the synthesis and demonstrate the self-assembly of pluronic F127 (PF127) on a cystamine–glutathione–MoS2 (CYS–GSH–MoS2) system, which can be used for GSH-triggered drug release under biological reducing conditions. The reduction-sensitive disulfide bond containing CYS was incorporated between the amphiphilic copolymer PF127 and GSH–MoS2 to achieve feasible drug release. Percent drug loading capacity and encapsulation efficiency were 51.3% and 56%, respectively. In addition, when the MoS2–GSH–CYS–PF127 nanocomposite was incubated in a GSH environment, the morphology of the nanocomposite tended to change, ultimately leading to drug release. The drug-loaded PF127–CYS–GSH–MoS2 polymeric nanocomposites efficiently released 52% of their drug content after 72 h of incubation in a GSH reduction environment. The HeLa cells treated with DOX loaded MoS2–GSH–CYS–PF127 showed 38% toxicity at drug concentration of 40 μg, which indicated that the successfully released of drug from carrier and caused the cell death. Further, fluorescence microscopy images of HeLa cells revealed the potential behavior of the MoS2–GSH–CYS–PF12 nanocomposite during the 2- and 4 h incubation periods; the nanocomposite was only found in the cytoplasm of HeLa cells. Interestingly, after 6 h of incubation, the drug was slowly released from the nanocomposite and could enter the nucleus as confirmed by fluorescence imaging of HeLa cells. Altogether, our synthesized PF127-coated MoS2 nanocomposite could be effectively adopted in the near future as a GSH-sensitive drug carrier.

Highlights

In the past decade, there has been a growing interest for the construction of a remarkable reduction-responsive drug delivery system (DDS).[1]
pluronic F127 (PF127) polymer coating reduced the size of the nanocarrier from size of MoS2–GSH–cystamine dihydrochloride (CYS) particle from 110.2 nm to 82.3 nm.[50,51]
By using the dialysis method, we demonstrated the release of DOX from MoS2–GSH–CYS–PF127 nanocomposites at 37 C in PBS buffer in the presence and absence of 5 mM GSH

Summary

Introduction

There has been a growing interest for the construction of a remarkable reduction-responsive drug delivery system (DDS).[1]. Two-D nanomaterials have uniquely been considered for biomedical application due to their outstanding electronic, physical, and chemical properties.[34] As the large surface area of 2D nanomaterials provides adequate area for loading responsive cargo biomolecules, they are favorable materials for stimuliresponsive biomedical applications.[35] In particular, MoS2, WS2, MoSe2, and WSe2 have been studied as a replacement for graphene due to some limitations of graphene such as loss of its native properties when exfoliated using n-butyllithium (n-BuLi) method, zero band gap, structural defects and so on.[36,37,38,39,40] As molybdenum (Mo) is an essential element for individual enzymes in cells and S is a universal biological element,[41,42] MoS2 was recently examined to elucidate its potential biomedical applications. A stimuliresponsive nanocarrier system with MoS2 is essential to achieve an on-demand DDS.[45]

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