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Open AccessFeature PaperArticle

Development and Mechanistic Insight into the Enhanced Cytotoxic Potential of Parvifloron D Albumin Nanoparticles in EGFR-Overexpressing Pancreatic Cancer Cells

1
CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
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Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Ctra. A2 km 33,600 Campus Universitario, 28871 Alcalá de Henares, Spain
3
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutics Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa
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Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
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CQB, CQE, Faculdade de Ciências, Universidade de Lisboa, Campo Grande 1749-016 Lisboa, Portugal
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CESAM, Universidade de Lisboa, Faculdade de Ciências, Campo Grande 1749-016 Lisboa, Portugal
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Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
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Centro de Química Estrutural, Instituto Superior Técnico, Departamento de Engenharia Química, Universidade de Lisboa,1049-001 Lisboa, Portugal
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IBEB, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1733; https://doi.org/10.3390/cancers11111733
Received: 5 October 2019 / Revised: 29 October 2019 / Accepted: 1 November 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
Pancreatic cancer is one of the most lethal cancers, with an extremely poor prognosis. The development of more effective therapies is thus imperative. Natural origin compounds isolated from Plectranthus genus, such as parvifloron D (PvD), have cytotoxic and antiproliferative activity against human tumour cells. However, PvD is a very low water-soluble compound, being nanotechnology a promising alternative strategy to solve this problem. Therefore, the aim of this study was to optimize a nanosystem for preferential delivery of PvD to pancreatic tumour cells. Albumin nanoparticles (BSA NPs) were produced through a desolvation method. Glucose cross-linking and bioactive functionalization profiles of BSA platform were elucidated and analysed using static lattice atomistic simulations in vacuum. Using the optimized methodology, PvD was encapsulated (yield higher than 80%) while NPs were characterized in terms of size (100–400 nm) and morphology. Importantly, to achieve a preferential targeting to pancreatic cancer cells, erlotinib and cetuximab were attached to the PvD-loaded nanoparticle surface, and their antiproliferative effects were evaluated in BxPC3 and Panc-1 cell lines. Erlotinib conjugated NPs presented the highest antiproliferative effect toward pancreatic tumour cells. Accordingly, cell cycle analysis of the BxPC3 cell line showed marked accumulation of tumour cells in G1-phase and cell cycle arrest promoted by NPs. As a result, erlotinib conjugated PvD-loaded BSA NPs must be considered a suitable and promising carrier to deliver PvD at the tumour site, improving the treatment of pancreatic cancer. View Full-Text
Keywords: pancreatic cancer; parvifloron D; nanoparticles; albumin; erlotinib pancreatic cancer; parvifloron D; nanoparticles; albumin; erlotinib
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Santos-Rebelo, A.; Kumar, P.; Pillay, V.; Choonara, Y.E.; Eleutério, C.; Figueira, M.; Viana, A.S.; Ascensão, L.; Molpeceres, J.; Rijo, P.; Correia, I.; Amaral, J.; Solá, S.; Rodrigues, C.M.P.; Gaspar, M.M.; Reis, C.P. Development and Mechanistic Insight into the Enhanced Cytotoxic Potential of Parvifloron D Albumin Nanoparticles in EGFR-Overexpressing Pancreatic Cancer Cells. Cancers 2019, 11, 1733.

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