Targeted Imaging And Therapy Of Breast Cancer Based On Multifunctional Nanoparticles With Mesoporous Structure

Breast cancer is the most common malignancy among women worldwide. Imaging techniques have played important roles in screening, early diagnosis, staging and treatment response assessment of breast cancer. Nanomaterials such as magnetic nanoparticles, gold nanoparticles and mesoporous nanoparticles have been widely used in biomedical field. Due to their distinct properties, these nanomaterials have shown bright prospects for MRI, photoacoustic imaging, optical imaging, drug delivery, gene therapy and photothermal therapy of tumor. Recently, designing theranostic nanocomposite with simultaneous imaging and therapy has been a new research hot. In this dissertation, we constructed two novel multifunctional nanoplatforms with mesoporous structure for targeted imaging and therapy of breast cancer.We prepared flavin mononucleotide (FMN) and polyethylenimine (PEI) modified Fe3O4@mTiO2 nanoparticles (Fe3O4@mTiO2/FMN-PEI), which possessed magnetic targeting, MRI, optical imaging, and siRNA binding ability, due to the presence of Fe3O4 core, FMN (a fluorescent probe) anchor, and PEI coating. This nanocomposite has a high siRNA transfection efficiency to breast cancer MCF-7 cells, which can get a further enhancement by a magnetic guidance. Moreover, the siRNA delivery events can be visualized by MRI and optical imaging. Survivin-siRNA delivered by this nanocomposite can cause significant knockdown of Survivin protein and induce considerable cell apoptosis by gene silencing. Similarly, magnetic targeting can enhance survivin-siRNA silencing effects. In addition, the tumor growth of MCF-7 tumor-bearing mice can be inhibited by survivin-siRNA delivered by this nanocomposite, which also can be visualized by MRI and optical imaging.We also developed novel, yolk-shell structured, hollow periodic mesoporous organosilica (HPMO) coated gold nanorods (GNRs). Due to high surface area and large pore size of HPMO, the synthesized GNRs@HPMO can be utilized to load drugs for tumor therapy. Moreover, GNRs@HPMO can be used for photothermal therapy and photoacoustic imaging due to the presence of GNRs. In addition, we exploit mesenchymal stem cells (MSCs) to deliver GNRs@HPMO so as to realize targeted imaging and therapy of breast cancer, because of the cells inherent tumor homing tendency. GNRs@HPMO has relatively high PTX loading efficiency and ideal photothermal efficacy. Both GNRs@HPMO and PTX loaded GNRs@HPMO (GNRs@HPMO-PTX) show no obvious cytotoxicity on MSCs. The internalization of MSCs to GNRs@HPMO or GNRs@HPMO-PTX does not affect their tumor-tropic property. The combined chemotherapy and photothermal therapy are confirmed after breast cancer MCF-7 cells and GNRs@HPMO-PTX loaded MSCs are co-cultured and further exposed to the near-infrared light. Moreover, GNRs@HPMO loaded MSCs injected into tumor can be clearly visualized by photoacoustic imaging, suggesting the possibility of this nanocomposite useful of in vivo imaging. Additionly, intratumoral injection of GNRs@HPMO-PTX loaded MSCs following by the irradiation induces tumor regression more obviously in MCF-7 tumor-bearing mice, demonstrating the synergistic photothermal therapy and chemotherapy in vivo.