Cisplatin@US-tube Carbon Nanocapsules for Enhanced
Wilson, Lon J.
Doctor of Philosophy
The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivelty, 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 garnered special attention in the area. This thesis details the preparation, characterization, and in vitro and in vivo 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 by a loading procedure that is reproducible, 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 spectroscopy (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. The anticancer activity of Pluronic-wrapped CDDP@US-tubes (W-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. Moreover, it has been shown that CDDP release from W-CDDP@US-tubes nanocapsules can be stimulated remotely by a radiofrequency (RF) field which disrupts the Pluronic coating to release CDDP. RF-induced release-dependent cytotoxicity of W-CDDP@US-tubes has been evaluated in vitro against two different liver cancer cell lines, Hep3B and HepG2, and found to exhibit superior cytotoxicity compared to W-CDDP@US-tubes not exposed to RF. Finally, in vivo biodistribution and therapeutic efficacy of the CDDP@US-tube material has been evaluated against three different breast cancer xenograft mouse (SCID/Bg) models, and found to exhibit greater efficacy in suppressing tumor growth than free CDDP for both a MCF-7 cell line xenograft model and a BCM-4272 patient-derived xenograft (PDX) model. The CDDP@US-tubes also demonstrated prolonged circulation time compared to free CDDP which enhances permeability and retention (EPR) effects resulting in significantly more CDDP accumulation in tumors, as determined by Platinum (Pt) analysis via inductively-coupled plasma mass-spectrometry (ICP-MS).
Cisplatin; Single-walled carbon nanotubes; Drug delivery; Breast cancer; Nanotechnology