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   Research Progress Made in Cancer Nanotechnology TEXT SIZE: A A A
——Metallofullerenol Nanoparticles Reverse Drug-Resistance of Cancer Cells

A paper titled “Metallofullerene Nanoparticles Circumvent Tumor Resistance to Cisplatin by Reactivating Endocytosis” was 
 
Sensitizing CP-r tumors to cisplatin treatment by [Gd@C82(OH)22]n nanoparticles in vivo, photo from CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety
published on Proceedings of the National Academy of Sciences, the United States of America (PNAS) on April 20, 2010.The scientific result was from the research team led by Prof. Yuliang Zhao, Institute of High Energy Physic (IHEP) and Prof. Xingjie Liang, National Center for Nanoscience and Technology (NCNST). They found that the surface modified Gd-metallofullerene nanoparticles could effectively circumvent tumor resistance to cisplatin by reactivating endocytosis.

There are several fatal hurdles in the clinic treatment of cancer, one of them is the drug resistance of cancer cells that make most anticancer medicines become less or without efficacy. In the previous studies, Zhao et al. have found that some unique characteristics of nanoparticles may make their interactions with biological systems in a more effective fashion to regulate the biological processes of cancer. Cisplatin is a commercial chemotherapeutic drug used in clinics. However, acquired resistance confines its application in chemotherapeutics of cancer. To overcome the acquired resistance to cisplatin, we exposed 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 pre-treatment 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 progress. The engineered nanoparticle may provide new strategy and solution to overcome some fatal hurdles of cancer treatment.

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, photo from CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety

 

Notes: Cancer Nanotechnology, using nanoscale materials or techniques to overcome the fatal hurdles incancer treatments or detections, is a newly emerging area.

 
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