Analytical strategies to study the formation and drug delivery capabilities of ferritin-encapsulated cisplatin in sensit
- PDF / 2,087,865 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 60 Downloads / 154 Views
RESEARCH PAPER
Analytical strategies to study the formation and drug delivery capabilities of ferritin-encapsulated cisplatin in sensitive and resistant cell models Daniel Turiel-Fernández 1 & Elisa Blanco-González 1 & Mario Corte-Rodríguez 1 & Joerg Bettmer 1 & Maria Montes-Bayón 1 Received: 13 December 2019 / Revised: 5 February 2020 / Accepted: 25 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract One of the limitations in the use of cisplatin is its low penetration into cells. In addition, some cells develop the so called resistance, a multifactorial event that decreases significantly the intracellular cisplatin concentration. To circumvent these limitations, recent studies are focused on the use of nanocarriers that permit, among others, to achieve higher drug uptake. In this work, ferritin is evaluated as a nanostructured cisplatin-delivery system in cell models of ovarian cancer. One of the key aspects is the characterization of the encapsulated product, and for this aim, a battery of analytical techniques, including size exclusion chromatography (SEC) coupled to UV detection and to inductively coupled plasma mass spectrometry (ICP-MS) together with transmission electron microscopy (TEM), is conducted. Higher level of incorporation occurs when using initial concentrations of the Fe-containing form of the protein at 10 mg/mL and 1 mg/mL cisplatin solution. The incorporation of the free and encapsulated cisplatin is addressed in A2780 and A2780CIS, sensitive and cisplatin-resistant cell lines, respectively, showing a significantly higher uptake of the encapsulated form. These values ranged from 5- to 9-fold in the sensitive line and 2–4 in the resistant model, being always more pronounced at the lower doses. Functionality of the drug after encapsulation is addressed by monitoring the presence of Pt in DNA and normalizing DNA concentration through simultaneous P and Pt measurements by ICP-MS. Time elapsed between exposure and Pt detection in DNA proved to be critical in the encapsulated model, showing the slower drug release mechanism from the ferritin nanocage that could be advantageously used for a controlled therapy. Keywords Encapsulation . Cisplatin . Ferritin . ICP-MS . DNA
Introduction Chemotherapy conventionally involves the use of synthetic molecules and natural products that in general are low molecular weight compounds. Such agents inherently suffer from suboptimal utilization due to rapid clearance and short blood Published in the topical collection featuring Female Role Models in Analytical Chemistry. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02549-0) contains supplementary material, which is available to authorized users. * Maria Montes-Bayón [email protected] 1
Department of Physical and Analytical Chemistry, Faculty of Chemistry and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, C/ Julian Clavería 8, 33006 Oviedo, Spain
circulation times [1, 2].
Data Loading...
