Uptake of CDDP-containing Polymeric Micelles by Cells Using Particle Induced X-Ray Emission

Abstract

Polymeric micelles loaded with cis-diamminedichloroplatinum(II), CDDP, (cisplatin micelles) enable higher accumulation in solid tumors and lower toxicities compared with CDDP alone. The combined use of cisplatin micelles with radiation is expected to enhance therapeutic effects and reduce side effects. The kinetics of cisplatin micelle uptake, however, have not been fully understood. Particle Induced X-Ray Emission has been employed in this study to measure the time transients of platinum in Chinese Hamster ovary cells. The results show that the platinum content of cells treated with cisplatin micelles increased more slowly than with CDDP alone, suggesting that cellular uptake could be controlled using micelles. The CDDP released from micelles was predominantly incorporated into the cells by diffusion. The uptake characteristics were further analyzed using micelles with different collapse rates. The results and techniques used in this study will be useful for designing an optimum treatment plan combining platinum-containing polymeric micelles and radiation in clinical applications.