Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. Among various types of breast cancer, the human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is known to be more aggressive and often resistant to medicinal treatment, leading to an insufficient prognosis and poor susceptibility to chemotherapy and/or hormonal therapy in the current clinic. These circumstances implicate that developing an improved therapeutic strategy rather than persistently changing the anticancer drugs for trying is truly needed to successfully cure this type of breast cancer. In this study, we aimed to fabricate anti-HER2 indocyanine green (ICG)-doxorubicin (DOX)-loaded polyethyleneimine-coated perfluorocarbon double nanoemulsions (HIDPPDNEs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer in vitro..

Results: The HIDPPDNE was first characterized as a sphere-like nanoparticle with surface charge of -57.1 5.6 mV and size of 340.6 4.5 nm, whereas the DOX release rates for the nanodroplets within 48h in 4 and 37 oC were obtained by 8.13 2.46% and 19.88 2.75%, respectively. We then examined the target-ability of the nanodroplets and found that the uptake efficiency of the HIDPPDNEs in HER2-positive MDA-MB-453 cells was approximately 2.5-fold higher than that in HER2-negative MCF7 cells, showing that the HIDPPDNEs were binding specific to HER2-expressing cells. In comparison to freely dissolved ICG, the HIDPPDNEs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared irradiation (808 nm; 6 W/cm2). Based on the viability analyses, the results showed that the HIDPPDNEs were effective on cell eradication upon near infrared irradiation (808 nm; 6W/cm2), and the resulting cell mortality was even higher than that caused by using twice amount of encapsulated DOX or ICG alone.

Conclusion: This work demonstrated that the HIDPPDNEs were able to provide improved ICG stability, target specificity, and enhanced anticancer efficacy compared to equal dosage of free ICG and/or DOX, showing a high potential for use in HER2 breast cancer therapy with reduced chemotoxicity.

Yu-Hsiang Lee received his B.S. degree in chemical engineering department from Tunghai University (Taiwan, ROC) in 1998, the M.S. degree in chemical engineering department from University of Southern California (USA) in 2002, and the Ph.D. degree in chemical engineering department from University of Southern California (USA) in 2006.