| Summary: | 碩士 === 國立中央大學 === 生物醫學工程研究所 === 104 === Breast cancer has long been recognized as one of the most lethal gynecological disease for women due to high drug resistance and serious side effects during treatment. To resolve these issues, a multi-functional human epidermal growth factor receptor 2 (HER-2)-targeted Indocyanine green (ICG)-Doxorubicin (DOX)-loaded perfluorocarbon double-nano-emulsion (HIDPDNE) was developed in this study. The size and surface charge of the HIDPDNE are 340 4.5 nm and -57 1.15 mV, respectively. The encapsulation efficiency for ICG and DOX is 95% and 60%, respectively. Under incubation at 37 oC for 24 h, the amount of entrapped ICG enhanced 5 folds as compared to the freely dissolved ICG and > 80 wt% of DOX remained in the particles, showing that the thermal stability of loaded chemicals in the aqueous solution is improved. Through the detection of ICG-induced fluorescence, we found that the uptake efficiency of HIDPDNEs within 4 h in MDA-MB-453 cells (HER-2+) was 4-fold higher than that in MCF7 cells (HER-2-), showing that the HIDPDNEs indeed have targeting specificity for HER2-expressing cells. In terms of the therapeutic functionality of the nano-agent, our data show that upon NIR laser exposure, the temperature of medium containing HIDPDNEs with ≥ 2-M ICG equivalent enabled to reach > 40oC within 90 sec and its amount of singlet oxygen yielded significantly enhanced ≥ 6 folds after 5-min laser treatment. The capacity of HIDPDNEs in cancer cell killing was further verified by using MDA-MB-453 as the model cell that the motality of the cells which were treated by HIDPDNEs with 10 and 4.68 M of ICG and DOX equivalent, respectively, for 4 h and followed by 5-min NIR light illumination significantly enhanced 1.8- (P < 0.05) and 2 folds (P < 0.05) as compared to the group with DOX alone or ICG + laser, respectively. Overall, the HIDPDNEs which enable to provide both chemo and photo therapies exhibit a high potential for use in destruction of breast tumor.
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