Immunotherapy: Open Access
Open Access
ISSN: 2471-9552
ISSN: 2471-9552
Michael R Shurin
University of Pittsburgh Medical Center, USA
Posters & Accepted Abstracts: Immunother Open Acc
Cellular and molecular interactions within the tumor microenvironment play the key role in regulating the tumor growth and progression, as well as in tumor response to therapy. The use of Nano vehicles 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 micro environmental conditions has not been investigated. Using murine lung cancer model, we demonstrated for the first time that aspiration of nanomaterials altered the lung microenvironment and accelerated in growth of lung carcinoma cells. The pro-tumorigenic effect of exposure to nanotubes was mediated by myeloid derived suppressor cells (MDSC) and TGF-�², as depletion of MDSC and the absence of the TGF-�² signaling significantly abrogated tumor stimulating effect of nanomaterials. We have also 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 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.
Email: shurinmr@upmc.edu