Enhanced antitumor efficacy of ultrasonic cavitation with up-sized microbubbles in pancreatic cancer
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Pintong Huang1, Ying Zhang1, Jian Chen2, Weihui Shentu1 , Yu Sun3, Zhijian Yang3, Tingbo Liang2, Shuyuan Chen4 and Zhaoxia Pu1
1 Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China
2 Department of Surgery, The Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China
3 Origin Biosciences Inc., Nanjing, Jiangsu Province, P. R. China
4 Baylor Research Institute, Baylor University Medical Center at Dallas, Texas, USA
Pintong Huang, email:
Keywords: ultrasonic cavitation; microbubbles; tumor vasculature; pancreatic cancer; therapy
Received: February 14, 2015 Accepted: April 22, 2015 Published: May 08, 2015
Ultrasonic cavitation is a novel potential approach for cancer treatment. We optimized the techniques of ultrasonic cavitation to enhance antitumor efficacy in a mouse model with human pancreatic cancer. A polydisperse MB contrast agent formulation (TS-P) with a mean number diameter of 1.9 μm was depleted in small diameter particles by differential centrifugation, producing an “up-sized” size distribution (TS-PL) possessing a mean diameter of 2.9 μm. Mice bearing the XPA-1-RFP pancreatic tumor were treated daily for 3 consecutive days with either up-sized or standard MB. Both treatment cohorts exhibited a significant reduction in tumor volume relative to the untreated control cohort (P < 0.05), and TS-PL group has significantly reduction in tumor volume (1215.1± 324.7 mm3) compared with standard TS-P group (2131.2±753.4 mm3) (P < 0.05). The treatment with TS-PL resulted in more tumor cell necrosis and apoptosis than with TS-P. Decreased expression of CD31 and MVD was observed histologically in tumors treated with TS-PL relative to TS-P. This study demonstrates that tuning the size distribution of existing contrast agent products, specifically to reduce the concentration of small MB, is required for enhanced anti-tumor cavitation activity.
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