Biomedical Dual-Action Imaging Probes for Cancer Therapy

本项目旨在合成一系列具有双重作用的新型抗癌药物治疗探针。这些化合物将包含基于咪唑的血红素加氧酶-1（HO-1）抑制剂和抗癌药物（例如PS，嵌入剂），沿着，以靶向更容易产生耐药性的肿瘤。HO-1调节细胞毒性游离血红素的浓度，但也已知其在过表达的癌症中具有防御作用。因此，抑制HO-1为治疗癌症提供了一种可能的替代策略。文献中的实例已经证明了使用组合疗法来克服癌症抗性，从而导致治疗有效性的增加。例如，Canti及其同事发现，AlS 2 Pc（一种用于光动力疗法的光敏剂（PS））和化疗药物（即阿霉素和顺铂）的组合给药对小鼠肿瘤产生了协同治疗作用。鉴于此，存在这样的可能性，即，在抑制HO-1活性的同时掺入用于光动力疗法的PS或用于化学疗法的嵌入剂的组合探针可以提高抗癌治疗的成功率。

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.