In vitro and in vivo imaging of peptide-encapsulated polymer nanoparticles for cancer biomarker activated drug delivery

Chemotherapy;Targeted drug delivery;Gelatin nanoparticles;Doxorubicin;In vivo ultrasound imaging

Kulsharova, Gulsim ; Liu ; Gang Logan

关键词: Chemotherapy;    Targeted drug delivery;    Gelatin nanoparticles;    Doxorubicin;    In vivo ultrasound imaging;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/31041/Kulsharova_Gulsim.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Cancer creates one of the most significant public health problems not just in the United States, but worldwide. While one of the most effective treatment protocols for cancer is chemotherapy, the conventional agents used in chemotherapy affect normal tissue as well as cancerous tissue. This thesis reports the development of a new cancer drug delivery system based on nanoparticles, which is designed to target tumor sites better than previous practices. In this study, nanoparticles coated with cathepsin D-specific peptides were developed as a vehicle for the targeted delivery of the cancer drug doxorubicin (DOX) to treat breast malignancy. Cathepsin D, a breast cancer cell secretion, triggers the release of DOX by digesting the protective peptide-coating layer of nanoparticles. Ultrasound imaging successfully detected fabricated nanoparticles in both in vitro conditions and in vivo mouse cancer models. Cell viability experiments were conducted to determine the efficacy of biomarker activation specific to breast cancer cell lines. These experimental results were compared with the outcome of a viability experiment run on non-cancerous cells. Viability decreased in human breast MCF7 cancer and mouse breast 4T1 cancer cells with no effect on fibroblast 3T3 non-cancerous cells. The next step was to obtain a real-time video of nanoparticle flow in mouse models using in-vivo ultrasound imaging. In vivo fluorescence imaging enabled the examination of cancerous mice injected with the drug-carrying nanoparticles. Results showed the distribution of nanoparticles in subject mice bodies, with concentrations in bladder and tumor sites. This finding suggests that nanoparticles are able to specifically target tumor tissues. It also suggests nanoparticles are resistant to nonspecific disintegration of peptide coating and consequential system drug release.Thus, the results of this work can be of great value for the development of more effective cancer treatment methods.