Cisplatin@US-tube carbon nanocapsules for enhanced chemotherapeutic delivery

Abstract

The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have also garnered attention in the area of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of a new ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectrometry (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 °C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic-F108 surfactant. Finally, the anticancer activity of pluronic-wrapped CDDP@US-tubes has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP after 24 h. These studies have laid the foundation for developing US-tube-based delivery of chemotherapeutics, with drug release mainly limited to within cancer cells only.

Figure 1

Preparation and purification of CDDP@US-tubes.

Figure 2

Pt determination by ICP-OES analysis of each collected aliquot of H₂O wash solution for a typical CDDP@US-tube sample. The data are expressed as mean ± SD of three independent experiment. Error bars may be smaller than symbols.

Figure 3

HR-TEM images of a) bundled CDDP@US-tubes and b) bundled empty US-tubes.

Figure 4

XPS spectrum of a) CDDP@US-tubes (survey), b) Pt 4f peaks for various samples: i) metallic platinum (Pt⁰), ii) CDDP@US-tubes (Pt²⁺) and iii) Na₂PtCI₆.6H₂O (Pt⁴⁺).

Figure 5

Comparative time release profiles of CDDP released from CDDP@US-tubes and W-CDDP@US-tubes (pluronic-F108-wrapped) in PBS at 37 °C. The data are expressed as mean ± SD of three independent experiments.

Figure 6

Time and concentration dependency of cell viability studies for MCF-7 and MDA-MB-231 cells incubated with CDDP, W-CDDP@US-tubes, and W-US-tubes. The quantity of US-tubes at each CDDP concentration is equivalent for the CDDP@US-tube and US-tube samples, with the concentration being calculated from their wt% values obtained by ICP-OES for Ni and Y which is contained within US-tube materials as the metal catalysts for carbon nanotube growth. The data are expressed as mean ± SD for three independent experiments. (*) and (^‡) indicate a statistically significant difference between W-CDDP@US-tube data compared to free CDDP data (*p < 0.01, ^‡p<0.05).