Biomedical Dual-Action Imaging Probes for Cancer Therapy

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This project aims to synthesize a series of dual-action therapeutic probes as novel anticancer agents. The compounds will incorporate an imidazole-based heme oxygenase-1 (HO-1) inhibitor along with an anti-cancer drug (e.g. PS, intercalating agent) to target tumors more susceptible to drug resistance. HO-1 regulates the concentration of cytotoxic free heme, but it is also known has a defensive role in cancers where it is overexpressed. Therefore, inhibiting HO-1 provides a possible alternative strategy in treating cancer. Examples in the literature have demonstrated the use of combinational therapy to overcome cancer resistance leading to an increased effectiveness in treatment. For example, Canti and co-workers discovered that the combinatorial administration of AlS2Pc, a photosensitizer (PS) used in photodynamic therapy, and chemotherapy drugs (i.e. Adriamycin and cisplatin) produced a synergistic therapeutic effect on murine tumors. In light of that, there is potential that a combinatorial probe that incorporates a PS for use in photodynamic therapy or an intercalating agent for use in chemotherapy while simultaneously inhibiting HO-1 activity can improve the success rate of the anticancer treatment.