Fabrication of HER2 Target Indocyanine Green-Camptothecin-Loaded Perfluorocarbon Nanodroplets for Photochemotherapy and Fluorescence Diffuse Optical Tomography of Breast Cancer

• Main Authors: Po-Wei Kuo, 郭柏緯
• Other Authors: Yu-Hsiang Lee
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/krgc5y

碩士 === 國立中央大學 === 生醫科學與工程學系 === 106 === HER2-expressing breast cancer has long been recognized as one of the most lethal gynecological disease for women due to high incidence, its drug resistance and poor prognosis. On the other hand, treatment of breast cancer in its early stage may dramatically enhance the 5-year survival rate to > 90 %, indicating that in addition to development of an effective therapeutic strategy, successful early detection plays a crucial role in the improvement of survival rate of HER2+ breast cancer. In this study, a type of theranostic agent named human epidermal growth factor receptor 2 (HER2)-target Indocyanine green (ICG)-Camptothecin (CPT)-loaded perfluorocarbon double-nanoemulsions (HICPDNEs) was developed for use in photochemotherapy and fluorescence diffuse optical tomography (FDOT) diagnostics. According to our result, the size and zeta potential of HICPDNEs is 292.2 ± 5.6 nm and -13.5 ± 3.1 mV, respectively. The encapsulation efficiency for CPT and ICG is 40.31 ± 7.6 % and 99.12 ± 0.33 %, respectively. Under incubated at 37 ℃ for 48 hr, The degradation of HICPDNEs almost prolong 73 % compared with Free ICG, and only 4.29 % drug release. Hyperthermia effect of HICPDNEs under 808 nm laser exposure with intensity of 6 W/cm2 for 5 min, 20 μM of HICPDNEs can achieve 42 ℃. To generation of singlet oxygen, HICPDNEs are higher than the free ICG enormously at the same concentration, showed the potential of the phototherapy. Compare to the ICPDNEs, HICPDNEs are more effective to combine the HER2+ breast cancer cell (MDA-MB-453) due to its target mechanism, indicated HICPDNEs has specification on HER2 positive cancer cell. In cytotoxicity, HICPDNEs incubated with cell for 16 hr and expose the 808 nm laser (6 W/cm2) for 5 min. its cell viability indicated good effective than the free CPT in high concentration (> 40 μM). In diagnosis, Tumor-like inclusions containing HICPDNEs in breast phantoms could be detected up to a depth of 4.5 cm using a FDOT system, according to 「Tumor resection quality index」, the best value is 24.89 in 1μM of HICPDNEs. Above of all, HICPDNEs has a good potential to be a theranostic agent for treatment and early diagnosis in breast cancer. More studies that we need to further validate in the future.