Lee Yu-Hsiang, Ma Yun-Ting
Department of Biomedical Sciences and Engineering, National Central University, No. 300, Jhongda Rd., Taoyuan City, 32001, Taiwan, ROC.
Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan, ROC.
J Nanobiotechnology. 2017 May 18;15(1):41. doi: 10.1186/s12951-017-0274-5.
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.
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 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/cm). Based on the viability analyses, the results showed that the HIDPPDNEs were effective on cell eradication upon near infrared irradiation (808 nm; 6 W/cm), and the resulting cell mortality was even higher than that caused by using twice amount of encapsulated DOX or ICG alone.
This 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.
乳腺癌是全球女性中最常被诊断出的癌症，也是癌症死亡的主要原因。在各种类型的乳腺癌中，人表皮生长因子受体2（HER2）过表达的乳腺癌已知更具侵袭性，且常常对药物治疗耐药，导致目前临床上预后不良，对化疗和/或激素治疗的敏感性较差。这些情况表明，真正需要制定一种改进的治疗策略，而不是一味地更换抗癌药物来尝试，以成功治愈这类乳腺癌。在本研究中，我们旨在制备负载抗HER2吲哚菁绿（ICG）-阿霉素（DOX）的聚乙烯亚胺包被的全氟碳双纳米乳液（HIDPPDNEs），以探索在体外对HER2过表达乳腺癌进行光疗和化疗联合给药的效果。
HIDPPDNE首先被表征为一种球形纳米颗粒，表面电荷为-57.1±5.6 mV，尺寸为340.6±4.5 nm，而纳米液滴在4℃和37℃下48小时内的DOX释放率分别为8.13±2.46%和19.88±2.75%。然后我们检测了该纳米结构的靶向能力，发现HIDPPDNEs与HER2+ MDA-MB-453细胞的黏附效率比没有抗HER2抗体的纳米液滴高三倍，表明HIDPPDNEs是具有HER2结合特异性的产物。与游离溶解的ICG相比，HIDPPDNEs赋予包裹的ICG更高的热稳定性，并且在近红外照射（808 nm；6 W/cm）下能够提供相当的热疗效果，并显著增加单线态氧的产生。基于活力分析，结果表明HIDPPDNEs在近红外照射（808 nm；6 W/cm）下对细胞清除有效，并且产生的细胞死亡率甚至高于单独使用两倍剂量的包裹DOX或ICG所导致的死亡率。
这项工作表明，与等量的游离ICG和/或DOX相比，HIDPPDNEs能够提供更好的ICG稳定性、结合特异性和增强的抗癌效果，显示出在HER2乳腺癌治疗中具有降低化学毒性的高应用潜力。
