Increased paclitaxel cytotoxicity against cancer cell lines using a novel functionalized carbon nanotube

Abstract

Potential applications of carbon nanotubes have attracted many researchers in the field of drug delivery systems. In this study, multiwalled carbon nanotubes (MWNTs) were first functionalized using hyperbranched poly citric acid (PCA) to improve their hydrophilicity and functionality. Then, paclitaxel (PTX), a potent anticancer agent, was conjugated to the carboxyl functional groups of poly citric acid via a cleavable ester bond to obtain a MWNT- g -PCA-PTX conjugate. Drug content of the conjugate was about 38% (w/w). The particle size of MWNT- g -PCA and MWNT- g -PCA-PTX was approximately 125 and 200 nm, respectively. Atomic force microscopy and transmission electron microscopy images showed a curved shape for MWNT- g -PCA and MWNT- g -PCA-PTX, which was in contrast with the straight or linear conformation expected from carbon nanotubes. It seems that the high hydrophilicity of poly citric acid and high hydrophobicity of MWNTs led to conformational changes from a linear state to a curved state. Paclitaxel can be released from the MWNT- g -PCA-PTX conjugates faster at pH 6.8 and 5.0 than at pH 7.4, which was suitable for the release of the drug in tumor tissues and tumor cells. In vitro cytotoxicity studies were evaluated in the A549 and SKOV3 cell lines. MWNT- g -PCA had an insignificant cytotoxic effect on both cell lines. MWNT- g -PCA-PTX had more of a cytotoxic effect than the free drug over a shorter incubation time (eg, 24 hours versus 48 hours), which suggests improved cell penetration of MWNT- g -PCA-PTX. Therefore, paclitaxel conjugated to MWNT- g -PCA is promising for cancer therapeutics.

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

“…In-vitro cytotoxicity studies in HeLa and MCF-7 cells showed both PX-loaded CNTs significantly increased cell death compared to free PX while the placebo CNTs were non-toxic. Recently Sobhani et al [180] functionalized multiple-walled CNTs using hyperbranched poly citric acid and conjugated PX on the CNTs. The drug loading was about 38% (w/w).…”

Preliminary study on conjugation of formononetin with multiwalled carbon nanotubes for inducing apoptosis via ROS production in HeLa cells

“…Consequently, CNTs have poor biocompatibility and high toxicity. 14 – 16 Therefore, it is crucial to modify CNTs through covalent or noncovalent functionalization of their external walls in order to improve their dispersion and stability, rendering them to be more biocompatible and less toxic. Functional CNTs can demonstrate improved properties for drug delivery including increased solubility, selectivity, blood circulation time, and uptake and accumulation within tumor cells.…”

Effect of Functionalized Carbon Nanotubes and their Citric Acid Polymerization on Mesenchymal Stem Cells In Vitro

“…Polycitric acid (PCA) [16,17,[26][27][28][29][30], a hyperbranched polymer with a highly biocompatible surface [16], has been proposed for building biological scaffolding and increasing the hydrophilicity of CNTs [17,28], reducing their aggregation and size polydispersity, and consequently diminishing their cytotoxicity [16,29,31]. Additionally, it has been found that PCA polymerization process does not generate pollutant particles [27].…”

“…The polymerization of MWNTs with PCA starts with the acid-functionalized MWNTs (fMWNT) and is followed by the addition of PCA, which covalently joins carboxylic functional groups of PCA and fMWNTs via a cleavable ester, obtaining polycitric acid-MWNTs (PMWNTs), an interesting material for nanomedicine applications [17,27,28,30,32]. Although in cell therapy, mesenchymal stem cells (MSCs) cultured on scaffolding are a real option in the field of tissue engineering [33] for generate or repair of new tissue [8,9,34,35], one of the major limitations is still the lack of anchoring between the damaged tissue and the cells that are supplied, because the MSCs applied by suspension directly in damaged areas produce little or null improvements on the surrounding damaged tissue [36] by transdifferentiation effect.…”