Anti-vascular Therapy via VEGFR2-targeted Microbubble Cavitation for Pancreatic Cancer Therapy

Tzu-Yun Chiu (邱子耘), Yi-Ju Ho

Department of Biological Science and Technology, National Yang Ming Chiao Tung University 

Tumor highly presents angiogenesis to growth rapidly with the overexpression of vascular endothelial growth factor receptor 2 (VEGFR2). Anti-vascular therapy is a treatment strategy to inhibit tumor growth via disrupting the existing abnormal vessels for starving tumors. However, the uneven efficiency of vascular disruption shows incomplete treatment leading to tumor recurrence by chemical anti-vascular agents. Therefore, our study used ultrasound combined with VEGFR2-targeted microbubbles (VMBs) to enhance the efficacy of anti-vascular therapy in pancreatic tumors. Under ultrasound stimulation, the mechanical force generated from VMB cavitation might cause physical vascular disruption, achieving the effect of anti-vascular therapy. Our homemade VMBs contained with C3F8 gas which were modified VEGFR2 antibody on the phospholipid shell via biotin-avidin interaction. Murine subcutaneous pancreatic tumor model (C57BL/6 implanted with Panc02 cells) was used to evaluate the targeting ability of VMBs when tumor volume reached to 50 mm3. After iv injection of VMBs (1×108 per mouse), tumor perfusion imaging was observed over time under ultrasound imaging system to evaluate the in vivo ability of tumor vessel targeting on VMBs. The fabrication of VMBs with average diameter of 573±52 nm and the average concentration of 5.51×1010 MBs/mL. The loading efficiency of VEGFR2 on VMBs was 60±6% (N=2). However, ultrasound imaging revealed non-significant enhancement of contrast within tumors in the VMB group relative to the control MB group. The intravital imaging observed from murine dorsal window chamber tumor model also revealed non-visualized targeting events of VMBs on tumor vessel wall. The subsequent modification of this study would be increasing the loading efficiency of VEGFR2 on VMBs for future investigation.