Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy

R. Domínguez-Ríos, D.R. Sánchez-Ramírez, K. Ruiz-Saray, P.E. Oceguera-Basurto, M. Almada, J. Juárez, A. Zepeda-Moreno, A. del Toro-Arreola, A. Topete, A. Daneri-Navarro

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)7707
Number of pages7714
JournalColloids and Surfaces B: Biointerfaces
Volume128
DOIs
StatePublished - 1 Jun 2019
Externally publishedYes

Cite this

Domínguez-Ríos, R., Sánchez-Ramírez, D. R., Ruiz-Saray, K., Oceguera-Basurto, P. E., Almada, M., Juárez, J., ... Daneri-Navarro, A. (2019). Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy. Colloids and Surfaces B: Biointerfaces, 128, 7707. https://doi.org/10.1016/j.colsurfb.2019.03.011
Domínguez-Ríos, R. ; Sánchez-Ramírez, D.R. ; Ruiz-Saray, K. ; Oceguera-Basurto, P.E. ; Almada, M. ; Juárez, J. ; Zepeda-Moreno, A. ; del Toro-Arreola, A. ; Topete, A. ; Daneri-Navarro, A. / Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy. In: Colloids and Surfaces B: Biointerfaces. 2019 ; Vol. 128. pp. 7707.
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abstract = "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.",
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Domínguez-Ríos, R, Sánchez-Ramírez, DR, Ruiz-Saray, K, Oceguera-Basurto, PE, Almada, M, Juárez, J, Zepeda-Moreno, A, del Toro-Arreola, A, Topete, A & Daneri-Navarro, A 2019, 'Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy', Colloids and Surfaces B: Biointerfaces, vol. 128, pp. 7707. https://doi.org/10.1016/j.colsurfb.2019.03.011

Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy. / Domínguez-Ríos, R.; Sánchez-Ramírez, D.R.; Ruiz-Saray, K.; Oceguera-Basurto, P.E.; Almada, M.; Juárez, J.; Zepeda-Moreno, A.; del Toro-Arreola, A.; Topete, A.; Daneri-Navarro, A.

In: Colloids and Surfaces B: Biointerfaces, Vol. 128, 01.06.2019, p. 7707.

Research output: Contribution to journalArticleResearchpeer-review

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.

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.

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Domínguez-Ríos R, Sánchez-Ramírez DR, Ruiz-Saray K, Oceguera-Basurto PE, Almada M, Juárez J et al. Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy. Colloids and Surfaces B: Biointerfaces. 2019 Jun 1;128:7707. https://doi.org/10.1016/j.colsurfb.2019.03.011