Overcoming the barriers of brain cancer treatment: targeted and fully nir absorbing photodynamic therapy agents with extremely low molecular weights and controlled lipophilicity
Cancer is the second leading cause of death worldwide, accounting for a total of 8.8 million deaths in 2015. Research efforts have resulted in significant increase in 5-year survival rates for some cancer types, however this is not the case in brain cancer. Three fundamental issues are at the core of this reality: 1) High percentage of inoperable brain tumours; 2) Limited number of drugs that can pass through the blood-brain barrier and 3) Absence of effective targeted brain cancer therapies. Photodynamic therapy (PDT) has the potential to be a selective, effective and non-invasive alternative to current treatments, however to date it is only applicable to a small group of cancers. Realization of non-toxic, water-soluble and photostable PDT agents, with strong near infrared absorption for deep tissue penetration, that also realizes high singlet oxygen generation efficiency and effective targeting, is the key for widespread use of PDT for majority of cancers. For brain cancer specifically, low molecular weights (Mws) and controlled lipophilicity is needed as well. The ultimate aim of INFRADYNAMICS is to create and validate the first series of advanced PDT agents that meet all these requirements and to demonstrate that a significant impact on brain cancer survival rates could be achieved. First, a series of advanced fluorophores that combine the two contradicting entities – absorption in NIR region (>700 nm) and low Mws – will be realized using novel design approaches which also allow a synthetically-viable pathway to tune lipophilicity. Then, appropriate heavy atom modifications for sensitization will be pursued. Most importantly, these sensitizers will be decorated with known and novel handles towards specific targeting of glioblastoma cells to attain the final PDT agents. Photophysical properties will be investigated, and finally, in-vitro and in-vivo studies will be performed to determine the effectiveness of our agents on brain cancer treatment.