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Research Progress on Metallofullerene Nanoparticles as Potential Effective Anti-cancer Medicine

Liang group at National Center for Nanoscience and Technology and Zhao group at Institute of High Energy Physics jointly found that metallofullerene nanoparticles could effectively circumvent tumor resistance to cisplatin by reactivating endocytosis (PNAS published ahead of print April 5, 2010, doi:10.1073/pnas.0909707107). Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C82(OH)22]n nanoparticles, that [Gd@C82(OH)22]n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of non-toxic [Gd@C82(OH)22]n not only decreased the number of surviving CP-r cells, but also inhibit growth of the CP-r tumors in athymic nude mice as measured by both optical and magnetic resonance imaging (MRI). Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CP-r PC-3-luc cells with [Gd@C82(OH)22]n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C82(OH)22]n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multi-drug resistance often found in cancer treatments. Further researches are still in study.

Nanoparticles activate endocytosis in the human chemotherapy-resistant cancer cells. Multihydroxylated metallofullerene nanoparticles are composed of amphiphilic fullerene derivative that encapsulates gadolinium as a core. The metallofullerene nanoparticles may circumvent cancer cells’ resistance to chemotherapeutical drugs by NP-enhanced endocytosis, thus increasing intracellular concentrations of the drugs.

(Xing-Jie Liang on April 6, 2010, NCNST)

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