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 (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 the cytotoxicity compared to the free POM, especially for the lower end of concentrations tested. 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.