According to the statistics every second person will be diagnosed with cancer during their lifetime. One out of every four will die because of this disease. Despite enormous knowledge improvement, the prognosis in cases with advanced tumors is still unsatisfactory. Firstly, only 1-2% of the administered drug is delivered to the solid tumor, while the rest goes to other tissues causing side effects. These 1-2% reaches predominantly well vascularized regions and therefore, solid tumors initially often respond well to conventional anti-cancer therapy decreasing the tumor mass. However, subsequent regrowth or metastasis after radio- or chemotherapy remains a serious problem in clinical oncology due to difficulties in penetration of the anticancer drug to the most hypoxic areas where cancer cells may remain. Moreover, chemotherapy or radiotherapy may cause additional formation of large hypoxic areas, making the treatment of tumor regrowth even more difficult. The fact that the efficacy of anticancer therapy is limited by the presence of hypoxic tumor cells has led to the introduction of a variety of therapeutic approaches aimed at elimination of these hypoxic areas. Therefore, improving drug delivery to hypoxic regions might be a ground breaking strategy in oncology. A key consequence of hypoxia is an increase in infiltration of macrophages, which undergo polarization toward tumor associated macrophages (TAMs) with M2 phenotype and paradoxically actively facilitate tumor development and spread to distant sites. Because macrophages are continuously recruited into the tumor mass and actively migrate to avascular and hypoxic regions, they represent attractive vehicles to deliver genes or other particles into the tumor.
The general objective of the project is to investigate novel macrophages-based delivery system of anticancer drugs encapsulated in ferritin cages into the hypoxic tumor areas and to investigate the underlying molecular mechanisms. Macrophages are physiologically attracted by the tumor, then they have ability to migrate from blood vessels and infiltrate avascular and hypoxic areas. Therefore they might constitute a unique delivery system of drug containing particles to the hypoxic parts of the tumor. Caged architecture of ferritin allows for efficient drug encapsulation. Macrophages are able to specifically and actively transfer ferritins (loaded with component of choice) to cancer cells. That macrophages loaded with ferritin containing anticancer drug could be an effective tool to smuggle drugs inside the tumor mass. The final effect will be the novel and effective macrophage-based delivery system of ferritin encapsulated drug that will constitute a starting point to development of a novel treatment strategy.
