Direct Correlation Between Zeta Potential and Cellular Uptake of Poly(methacrylic acid) Post-Modified with Guanidinium Functionalities

Cellular uptake is identified as one of the key parameters to the successful delivery of drugs into cancer cells. In this study, the effect of the ratio of negative and positive charges on a polymer on the amount of uptake is studied. Poly(methacrylic acid), prepared by RAFT polymerization, is post-functionalized with agmatine in water to various degrees. When agmatine ratio is increased to 1, the conjugation efficiency is observed to be ≈63% indicating potentially some steric hindrance or excessive repulsion by the positive charged guanidinium functionality. The resulting zeta potential, ranging from −40 to −14 mV, is in linear correlation with the degree of functionalization. The resulting polymers are found to be non-toxic to A2780 ovarian cancer cells. The cellular uptake is subsequently studied by laser scanning confocal fluorescent microscopy, flow cytometry, and by analysis of the fluorescence intensity of the remaining solution after incubation with A2780 ovarian cancer cells. An almost linear relationship between zeta potential and cellular uptake is observed. (Figure presented.)