Abstract
One of the greatest challenges of modern medicine is to find cheaper and easier ways to produce transporters for biologically active substances, which will provide selective and efficient drug delivery to the target cells, while causing low toxicity towards healthy cells. Currently, metal-based nanoparticles are considered a successful and viable solution to this problem. In this work, we propose the use of novel synthesis method of platinum nanoparticles (PtNPs) connected with their precise biophysical characterization and assessment of their potential toxicity. To work as an efficient nanodelivery platform, nanoparticles should interact with the desired active compounds spontaneously and non-covalently. We investigated possible direct interactions of PtNPs with ICR-191, a model acridine mutagen with well-established biophysical properties and mutagenic activity, by Dynamic Light Scattering, fluorescence spectroscopy, and Isothermal Titration Calorimetry. Moreover, to determine the biological activity of ICR-191-PtNPs aggregates, we employed Ames mutagenicity test, eukaryotic cell line analysis and toxicity test against the model organism Caenorhabditis elegans. PtNPs’ interesting physicochemical properties associated to the lack of toxicity in a tested range of concentrations, as well as their ability to modulate ICR-191 biological activity, suggest that these particles successfully work as potential delivery platforms for different biologically active substances.
Highlights
For many years, platinum compounds have been broadly used as antineoplastic agents in diverse types of cancer treatment therapies
The novel synthesis method proposed here differs from the already existing methods, as it is a less time and money consuming procedure, as it uses reagents found to be less aggressive for the environment
The Z-average value measured for platinum nanoparticles (PtNPs) mixture, an overall average size of aggregates in a tested solution, reaches 62.49 nm when the concentration of nanoparticles was equal to 0.16 μg/mL (Fig. 1B)
Summary
Platinum compounds have been broadly used as antineoplastic agents in diverse types of cancer treatment therapies (mostly as PtII coordination complexes, such as cisplatin, carboplatin, oxaliplatin, nedaplatin, lobaplatin, and heptaplatin). Their mechanism of action relays on platinum ions forming bonds with DNA bases, which causes DNA helix damage, arrest of the cell cycle and consequent apoptotic death. After entering the cell through passive diffusion, PtNPs exert size, concentration and time-dependent toxicity, caused by the introduction of strand breaks in the DNA It leads to the inhibition of replication, cell growth arrest, and apoptosis. The PtNPs synthesis techniques described in the literature so far are time and cost consuming, involving innumerous reaction steps and bulky equipment[3,10,16,18,20]
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