Myeloid Regulatory Cells and Nano-Delivery of Chemotherapeutic Agents

The use of nanovehicles for drug delivery is a promising and widely investigating approach to cancer therapy. However, the behavior of nanomaterials and carried chemotherapeutic agents in the local tumor microenvironmental conditions has not been investigated. We have revealed that chemotherapeutic agents, such as doxorubicin, can lose the antitumor activity in the myeloperoxidase-catalyzed and peroxynitrite-mediated oxidative conditions reflecting the activity of tumor-activated myeloid-derived suppressor cells (MDSC). Our data also suggests that the chemotherapeutic agents delivered by the nanocarrier, which constitutes an oxidized single-walled nanotube and a branched phospholipid-polyethylene glycol, may be protected from the enzymatic inactivation associated with myeloid cells in the tumor microenvironment while exhibiting the constant doxorubicin release rate. Additional development of nano-delivery system allowed generating unique carbon nanotube cups, i.e., nanoscale containers, that can be loaded with chemotherapeutic agents, corked with gold nanoparticles and be opened by MDSC-derived myeloperoxidase-catalyzed reactive intermediates and sodium hypochlorite. This results in local release of chemotherapeutic drugs in the MDSC-enriched microenvironment, i.e., the tumor milieu, and effective inhibition of MDSC activity. Thus, understanding the biology of myeloid regulatory cells in the tumor microenvironment opens new opportunity for development of effective and controllable nanocarrier for safe delivery of therapeutic agents to the tumor site.