Characterization and in vitro studies of the anticancer effect of oxidized carbon nanotubes functionalized with betulinic acid

Abstract

Among the array of nanomaterials, carbon nanotubes have shown great potential as drug carriers in the field of nanomedicine, owing to their attractive physicochemical structure, which facilitates functionalization of therapeutic molecules onto their external walls or being encapsulated inside the tubes. The aim of this preliminary study was to formulate betulinic acid (BA), a poorly water-soluble drug, in oxidized multiwalled carbon nanotubes (MWCNT-COOH) for enhanced delivery efficiency into cancer cells with reduced cytotoxicity. The synthesized MWCNT-BA nanocomposite was characterized using ultraviolet-visible, Fourier transform infrared, thermogravimetric analysis, powder X-ray diffraction, and field emission scanning electron microscopy techniques. The loading of BA in MWCNT-COOH nanocarrier was estimated to be about 14.5%–14.8% (w/w), as determined by ultraviolet-visible and thermogravimetric analysis. Fourier transform infrared study shows that the peaks of the resulting MWCNT-BA nanocomposite correlate to the characteristic functional groups of BA and MWCNT-COOH. The powder X-ray diffraction results confirmed that the tubular structures of MWCNT-COOH were not affected by the drug loading mechanism of BA. The release profiles demonstrated that approximately 98% of BA could be released within 22 hours by phosphate-buffered saline solution at pH 7.4 compared with about 22% within 24 hours at pH 4.8. The biocompatibility studies revealed that MWCNT-BA at concentrations <50μg/mL expressed no cytotoxicity effects for mouse embryo fibroblast cells after 72 hours of treatment. The anticancer activity of MWCNT-BA was observed to be more sensitive to human lung cancer cell line when compared with human liver cancer cell line, with half maximal inhibitory concentration values of 2.7 and 11.0μg/mL, respectively. Our findings form a fundamental platform for further investigation of the MWCNT-BA formulation against different types of cancer cells.

Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer

“…Our results also revealed excellent sustained release profiles, characterized by a slower slope, indicating that oMWCNTs-PEG were able to overcome the burst effect of free VP-16. This is one of the major general requirements for nanocarriers for drug delivery and numerous studies demonstrated similar release kinetics using MWCNTs bearing various anti-cancer agents [30][31][32]. In addition, a decrease in pH imitating the hypoxic microenvironment of the most solid tumors triggered faster release of VP-16 and Bcl-2 Aso from oMWCNTs-PEG hybrid nanocarrier.…”

Preparation, Characterization, andIn VitroandVivoAntitumor Activity of Oridonin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group

“…It was shown that MWCNT-BA demonstrated moderate cell growth inhibitory activity to HepG-2 in a concentrationdependent manner. The IC 50 of MWCNT-BA in HepG-2 cells was 11.0 g/mL, and this value was below that of free BA (IC 50 = 15.0 g/mL) [9]. The results showed that functionalized MWCNT held great potential in the field of nanobiotechnology and nanomedicine.…”

“…It becomes essential that the hydrophilic groups are introduced onto the hydrophobic surface of CNTs to improve their surface properties for enhanced dispersion, solubilization, biocompatibility, and reduced cytotoxicity [8]. Tan et al formulated betulinic acid (a poorly water-soluble drug) in MWCNTs-COOH to improve delivery efficiency into cancer cells while reducing cytotoxicity [9].…”

Therapeutic applications of betulinic acid nanoformulations

“…Tan et al . developed BA MWCNTs by noncovalent attachment of BA to MWCNT‐COOH through π−π stacking interactions and hydrogen bonds between –OH and –COOH groups . The in vitro cytotoxicity of the developed BA–MWCNTs demonstrated enhanced cytotoxicity compared with native BA in A549 and HepG2 cell lines.…”