Interventionl Molecular Imaging-Guided Precise Diagnosis And Treatment Of Breast Cancer

Breast cancer is the most common malignancy in women worldwide, with the mortality of III-IV-stage breast cancer more than 50%. Breast cancers are highly heterogeneous, comprising different responses to therapies due to various histological sub-types, immune phenotypes, as well as various gene expression and mutation patterns. Thus, there is a great prospect for early diagnosis and precise treatment of breast cancer. In this thesis, we primarily focus on validating an new concept, "Interventional molecular imaging-guided, radiofrequency (RF)-enhanced local chemotherapy", with the final aim of improving management of breast cancers by simultaneous integration of advanced technologies, including interventional oncology, radiofrequency (RF) technology, nanotechnology, and molecular imaging.The main contents and conclusions of this dissertation are as follows:Part 1:To the best our knowledge, this was the first attempt of using molecular imaging to guide interventional radiofrequency heat (RFH)-enhancedlocal chemotherapy of breast cancer. Through serial in-vitro experiments, we have successfully established the "proof-of-principle" of the new concept, intratumoral RFH-enhanced killing effects of chemotherapeutics on human breast cancer cells. Then, via serial in-vivo experiments, we have successfully validated the feasibility of the new technique, molecular MRI-guided, intratumoral RFH-enhanced direct chemotherapy of these breast cancers on living animals.Part 2:In this study, we first constructed novel photoluminescent mesoporous silica nanoparticles (MSN) at different diameters of 65,170, and 290 nm, which were fabricated by facile introduction of CaF2:Tm, Yb nanocrytal into the mesopores via a chemical assistant sol-gel in-situ growth method. The remaining spaces of mesopore channels were used as carriers of chemotherapeutic agents. Through a series of comprehensive in-vitro experiments, we have successfully confirmed that this design of chemotherapeutic-carrying MSN not only provided better chemodrug delivery to targets, but also resulted in low toxicity to surrounding healthy tissues.The results for these studies demonstrate the success of integrating advanced technologies, including radiofrequency technology, intervenitonal oncology, molecular imaging, nanotechnology and direct intratumoral chemotherapy, for further improving the managenet of breast cancer.