期刊
THERANOSTICS
卷 7, 期 2, 页码 253-269出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.16681
关键词
Cancer; Theranostic; Nanoparticle; CA4P; EPR; Desmoplastic; Cisplatin
资金
- National Science Foundation
- Dissertation Completion Fellowship from the Graduate School at the University of North Carolina at Chapel Hill
- NIH [CA149363, CA151652, CA149387]
Aggressive, desmoplastic tumors are notoriously difficult to treat because of their extensive stroma, high interstitial pressure, and resistant tumor microenvironment. We have developed a combination therapy that can significantly slow the growth of large, stroma-rich tumors by causing massive apoptosis in the tumor center while simultaneously increasing nanoparticle uptake through a treatment-induced increase in the accumulation and retention of nanoparticles in the tumor. The vascular disrupting agent Combretastatin A-4 Phosphate (CA4P) is able to increase the accumulation of radiation-containing nanoparticles for internal radiation therapy, and the retention of these delivered radioisotopes is maintained over several days. We use ultrasound to measure the effect of CA4P in live tumor-bearing mice, and we encapsulate the radio-theranostic isotope (177)Lutetium as a therapeutic agent as well as a means to measure nanoparticle accumulation and retention in the tumor. This combination therapy induces prolonged apoptosis in the tumor, decreasing both the fibroblast and total cell density and allowing further tumor growth inhibition using a cisplatin-containing nanoparticle.
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