A facile modification of single walled carbon nanotubes via diels-alder reaction for highly effective therapy

Journal of Science and Technology, Vol. 39A, 2019

© 2019 Industrial University of Ho Chi Minh City

A FACILE MODIFICATION OF SINGLE WALLED CARBON NANOTUBES

VIA DIELS-ALDER REACTION FOR HIGHLY EFFECTIVE THERAPY

XUAN THANG CAO

Faculty of Chemical Engineering, Industrial University of Ho Chi Minh City;

[email protected]

Abstract. In this study, a green and direct modification of poly(ethylene glycol)-graft-[furfuryl-graft-

(poly(styrene-alt-maleic anhydride))] (PEG-PSMF) on the surface of SWCNT was presented in aqueous

media through Diels-Alder click reaction. The obtained hybrid materials possessed a high drug loading

capacity of doxorubicin in comparison with other doxorubicin delivery vehicles, which could reach up to

279.9 wt.% of drug loading capacity. Moreover, in vitro drug release profiles showed that drug release

rate under an acidic condition of tumor cell microenvironment at pH 5.5 is much higher than under

physiological condition at pH 7.4. Cytotoxicity assays (MTT) demonstrated that the composite materials

did not have any practically cytotoxicity against the normal HEK293 cell line while they displayed a high

antitumor activity towards HeLa cancer cells. This strategy offers a promising SWCNT-based drug

carrier for tumor-targeted chemotherapy.

Keywords. carbon nanotubes, poly(ethylene glycol), Diels-Alder click, doxorubicin, HeLa cells.

1 INTRODUCTION

Recently, nanocarriers for low-molecular-weight drugs have proposed a promising strategy for

improving body distribution and prolonging blood circulation [1]. Among them, carbon nanotubes

(CNTs) would appear to be potential candidates [2]. According to the number of graphene layers from

which a single nanotube is composed, CNTs are categorized into single-walled carbon nanotubes

(SWCNT) and multi-walled carbon nanotubes (MWCNT) [3]. SWCNT diameter varies between 0.4–3

nm and are shaped in three distinct structures as armchair, zigzag, and chiral configurations, and

compared to MWCNT, SWCNT tend to exhibit richer electrical and optical properties [4]. The hollow

space inside SWCNT or the functionalized derivative outside SWCNT is likely to be an efficient drug

carrier in vivo [5,6]. In addition, with special sp2

-hybridized carbon surfaces and a large surface area

(theoretically 1300 m2

/g), SWCNT have a high capacity for drug integrating onto the surface of SWCNT

[7,8]. However, the biggest drawback of SWCNT is their extremely low solubility, pristine SWCNT

cannot circulate well in biological systems. The solubilization of SWCNT in aqueous medium can be

improved by either the presence of non-covalent dispersing agents or covalent modification of SWCNT

[9]. The external surface of SWCNT could be functionalized by non-covalent binding of therapeutic and

diagnostic agents [10,11]. Many synthetic polymers such as phospholipid-poly(ethylene glycol),

poly(phenylacetylene) and natural polymers such as polysaccharides have been also used to encase

SWCNT via non-covalent interactions improving their compatibility with water and physiological

environments more generally [12].

In this sense, Diels-Alder (DA) “click” chemistry, a moderate reaction without surface pretreatment of

CNTs, has emerged as a promising alternative to acidic oxidation because of its balance between the

preservation of intrinsic properties and the improvement of dispersibility of CNTs [13,14]. The DA

reaction-based surface modification is a strategy with advantages of simplicity, non-catalysis, solvent￾tolerant [15-22]. Thus, the utilization of DA for functionalization of CNTs is necessary to open a facile

route in synthesis of nanomaterials. Recently, the incorporation of polyethylene glycol (PEG) has been

studied to improve CNTs dispersibility in water and to decrease CNTs toxicity [23]. Till date, PEG

grafted SWCNT using DA reaction has not been reported.