Decorated carbon nanotubes as vectors to boost the effect of an anticancer drug from synthesis to in vivo results

This project has concerned the preparation, the characterization, and the biological testing of a drug delivery system based on decorated carbon nanotubes, aimed to the transport an anticancer drug inside cancer cells. Multi-walled carbon nanotubes have been modified to deliver doxorubicin inside cancer cells, resulting in an enhanced chemotherapic effect respect to the free drug. Decoration of the carbon nanotubes was accomplished through both covalent and non-covalent approaches: versatile click reactions and π-π interactions were exploited. To assess the internalization of the carbon nanotubes inside cells, a decoration with a fluorescent molecule, namely BODIPY, was performed. Next, the nanotubes were decorated with a selector molecule, biotin, to increase the uptake of the system by cancer cells. The non-toxicity of the simple delivery system alone (without drug) as well as the role of the selector have been investigated by parallel biological tests. Finally, the decorated system was loaded with the drug: doxorubicin. Comparative studies were performed on the loaded drug delivery system to highlight its effect respect to the free drug and to mark the role of the selector in the internalization efficiency. The overall project was composed by two parts: a) a comprehensive study of synthesis and characterization on the fluorescent probes suitable for the decoration of carbon nanotubes, with preliminary biological tests, and b) modification of carbon nanotubes and their decoration with a selector and the drug. The second part was complemented by extensive biological tests. In the first part boron dipyrromethene complexes (BODIPY) were synthesized and fully characterized, giving a series of novel fluorescent probes able to cover a large part of the absorption and emission visible spectra. Fluorescent molecules were also equipped with functional groups for the decoration of the nanotubes. The biological tests performed confirmed that the fluorescent nanotubes were easily located inside different model cancer cells. The biological data on internalization were obtained through confocal microscopy analysis and cytofluorimetric tests. In the second part, the drug delivery system has been completed with biotin as selector molecule and with doxorubicin. Finally, the system was tested again in vitro on breast cancer cells MCF-7 and in vivo on nude mice xenograft model. In both cases, comparative assays have been carried out with free doxorubicin, providing remarkable results. The adoption of biotin-decorated carbon nanotubes as vector to boost the drug internalization process has resulted into increasing the chemotherapic efficiency of doxorubicin, both in cellular models and animal models.