Polyoxometalate-Loaded Carboxymethyl Chitosan Nanoparticles with Anticancer Activity

Nanoparticles composed of selected polyoxometalates (POMs) and carboxymethyl chitosan (CMC) were prepared, characterized, and tested for anticancer activity to establish structure-activity relationships. Cell viability was investigated immediately after treatment and after 24 h to assess both cell recovery and delayed cytotoxicity. The study focused on three questions: (a) trends in cytotoxicity based on POM nuclearity and heteroatoms, (b) effects of CMC encapsulation strategies on cytotoxicity and cellular uptake, and (c) cell viability after a recovery period. Among polyoxotungstates, [NaP5W30O110]14-, with a high tungsten content, showed the greatest cytotoxicity towards PC-3 cells at low concentrations. [Co4(H2O)2(PW9O34)2]10- demonstrated moderate cytotoxicity with an IC50 of 437 ± 23 μM for MRC-5 cells, compared to 11 ± 0.3 μM for [NaP5W30O110]14-. Both POMs were encapsulated in a CMC matrix, forming nanoparticles of 100-250 nm, and analyzed by FT-IR and Raman spectroscopy, DLS, and cryo-TEM, and tested against MRC-5, PC-3, and HeLa cells. It was found that forming nanoparticles increased the magnitude of cytotoxicity compared to the free POM, especially for the lower end of the concentrations tested. However, ICP-MS analyses did not point to significant differences between the uptake of tungsten in cells treated with 250 μM [Co4(H2O)2(PW9O34)2]10- compared to the corresponding nanoparticle system. Furthermore, we newly monitored the cell viability after a 24 h rest period without treatment, allowing for observations of delayed negative or positive effects on the cells. This thorough approach revealed that the preparative strategy applied for encapsulation of [Co4(H2O)2(PW9O34)2]10- in CMC selectively influences the toxicity against HeLa and PC-3 cells compared to the normal MRC-5 cell line.