Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Xing Jie Liang, Huan Meng, Yingze Wang, Haiyong He, Jie Meng, Juan Lu, Paul C. Wang, Yuliang Zhao, Xueyun Gao, Baoyun Sun, Chunying Chen, Genmei Xing, Dingwu Shen, Michael M. Gottesman, Yan Wu, Jun Jie Yin, Lee Jia

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

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 nontoxic [Gd@C82(OH)22]n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and 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 multidrug resistance often found in cancer treatments.

Original languageEnglish (US)
Pages (from-to)7449-7454
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number16
DOIs
StatePublished - Apr 20 2010

Keywords

  • Chemotherapy
  • Drug resistance
  • Nanoimaging
  • Nanomedicine
  • Nanopharmaceutical

ASJC Scopus subject areas

  • General

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