Discovery of a Drug Delivery System Based on Carbon Nanotubes: Synthesis and Biological Studies

A drug delivery system (DDS) based on short oxidized multiwalled carbon nanotube has been prepared and tested for combined therapy. The DDS was loaded with metformin and doxorubicin, two antitumor drugs with different action mechanisms and targeting different kind of tumor cells. The DDS revealed efficient both in-vitro and in-vivo with 4T1 tumor-bearing mice, a challenging model for triple negative breast cancer. The DDS was modified to host radioactive tags to enable PET imaging. For this purpose, a new protocol for the labeling with radiometals was developed. The labeled materials were used to evaluate biodistribution of the nanostructure in 4T1 tumor-bearing mice. The biodistribution profile changed consistently depending on mode of administration, allowing the maximization of efficacy. To complete the study, the target engagement on oxidative phosphorylation was also investigated using [18F]Faza imaging of hypoxia on 4T1 tumor-bearing mice.