Abstract
BackgroundBreast 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.ResultsThe 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 48 h in 4 and 37 °C were obtained by 8.13 ± 2.46% and 19.88 ± 2.75%, respectively. We then examined the target-ability of the nanostructure and found that the adhesion efficiency of the HIDPPDNEs onto HER2+ MDA-MB-453 cells was threefold higher than the nanodroplets without anti-HER2 antibody, indicating that the HIDPPDNEs are the product with HER2 binding specificity. 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; 6 W/cm2), and the resulting cell mortality was even higher than that caused by using twice amount of encapsulated DOX or ICG alone.ConclusionsThis work demonstrates that the HIDPPDNEs are able to provide improved ICG stability, binding specificity, and enhanced anticancer efficacy as compared to equal dosage of free ICG and/or DOX, showing a high potential for use in HER2 breast cancer therapy with reduced chemotoxicity.
Highlights
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, which accounts for approximately 30% of breast cancer patients and locates in either primary tumors or metastatic sites, is known to be more aggressive and often resistant to medicinal treatment [3, 4], leading to an insufficient prognosis [5, 6] and poor susceptibility to chemotherapy and/or hormonal therapy [7] 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
The fluorescence level of the HIDPPDNEs with F-immunoglobulin G (IgG)-SAb was approximately 2.2-fold (P < 0.05) higher than that obtained from the F-IgG-SAbtreated IDPPDNEs (Fig. 2III, inset image c), showing that the enhanced fluorescence expression in the former group was mainly contributed from the first-secondary antibody conjugation instead of F-IgG-SAb-PEI electrostatic adsorption. These results clearly show that the HIDPPDNEs have an affinity to the corresponding secondary antibody, indicating that the anti-HER2-monoclonal antibody (mAb) were certainly bound on the surface of the HIDPPDNEs and were able to provide intact bioconjugation activity after the electrostatic assembling process
Summary
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. Among various types of breast cancer, the human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, which accounts for approximately 30% of breast cancer patients and locates in either primary tumors or metastatic sites, is known to be more aggressive and often resistant to medicinal treatment [3, 4], leading to an insufficient prognosis [5, 6] and poor susceptibility to chemotherapy and/or hormonal therapy [7] 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. No matter which mechanism is employed, the photosensitizer plays a key role in the effect of phototherapy
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