TY - JOUR
T1 - Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy
AU - Domínguez-Ríos, R.
AU - Sánchez-Ramírez, D.R.
AU - Ruiz-Saray, K.
AU - Oceguera-Basurto, P.E.
AU - Almada, M.
AU - Juárez, J.
AU - Zepeda-Moreno, A.
AU - del Toro-Arreola, A.
AU - Topete, A.
AU - Daneri-Navarro, A.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.
AB - The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.
KW - Cisplatin
KW - Drug release
KW - Ovarian cancer
KW - PLGA nanoparticles
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85062547003&partnerID=MN8TOARS
U2 - 10.1016/j.colsurfb.2019.03.011
DO - 10.1016/j.colsurfb.2019.03.011
M3 - Artículo
C2 - 30856589
SN - 0927-7765
VL - 128
SP - 7707
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -