September 18, 2006
Nanoparticles Boost Delivery of Cisplatin to Tumor Cells
Cisplatin is one of the most powerful and effective drugs for treating a wide variety of cancers, but many tumors develop resistance to this drug, ultimately limiting its benefits for cancer patients. Now, however, researchers have developed a nanoparticulate formulation of cisplatin that shows promise for overcoming drug resistance while boosting the amount of drug that accumulates inside malignant cells.
Reporting its work in the journal Langmuir, a team of investigators led by Ratnesh Lal, Ph.D., of the University of California, Santa Barbara, describes its development and characterization of a nanoscale liposome capable of ferrying cisplatin across the cell membrane of tumor cells. Using atomic force microscopy (AFM), the researchers were able to fully characterize the size distribution, drug encapsulation efficiency, stability, and cell uptake of their cisplatin liposomes.
The investigators identified several key physical characteristics, all easily measured using AFM, that enabled them to accurately measure cisplatin encapsulation in the liposomes. Past efforts by many research groups to encapsulate cisplatin within a liposome were judged unsuccessful, in part because of the difficulty in tracking the efficiency of drug encapsulation. In this case, the researchers found that the stiffness of any given liposome, measured using AFM force mapping, correlated with the amount of cisplatin encapsulated within that liposome.
By adding a fluorescent label to the liposomes, the investigators were able to monitor uptake by ovarian cancer cells growing in culture and to track their cell-killing properties. These studies showed that the cisplatin-loaded liposomes crossed the cell membrane in large numbers. More importantly, massive cell death occurred as a result, particularly when the cells were treated with smaller cisplatin-loaded liposomes, i.e., those with diameters less than 250 nanometers.
This work is detailed in a paper titled, “Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity.” Investigators from Richmond Chemical Corporation also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website.