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. This evidence concerns the gene ERBB2 and breast carcinoma.