American Association for Cancer Research
00085472can113232-sup-fig_1.pdf (50.31 kB)

Supplementary Figure 1 from Ultrasound Increases Nanoparticle Delivery by Reducing Intratumoral Pressure and Increasing Transport in Epithelial and Epithelial–Mesenchymal Transition Tumors

Download (50.31 kB)
journal contribution
posted on 2023-03-30, 21:33 authored by Katherine D. Watson, Chun-Yen Lai, Shengping Qin, Dustin E. Kruse, Yueh-Chen Lin, Jai Woong Seo, Robert D. Cardiff, Lisa M. Mahakian, Julie Beegle, Elizabeth S. Ingham, Fitz-Roy Curry, Rolf K. Reed, Katherine W. Ferrara

PDF file - 51K, Representative biodistribution of tissues 48 hours after nanoparticle injection (N=8). Accumulation was significantly greater for insonified tumors (p<0.001).



Acquisition of the epithelial–mesenchymal transition (EMT) tumor phenotype is associated with impaired chemotherapeutic delivery and a poor prognosis. In this study, we investigated the application of therapeutic ultrasound methods available in the clinic to increase nanotherapeutic particle accumulation in epithelial and EMT tumors by labeling particles with a positron emission tomography tracer. Epithelial tumors were highly vascularized with tight cell–cell junctions, compared with EMT tumors where cells displayed an irregular, elongated shape with loosened cell–cell adhesions and a reduction in E-cadherin and cytokeratins 8/18 and 19. Without ultrasound, the accumulation of liposomal nanoparticles administered to tumors in vivo was approximately 1.5 times greater in epithelial tumors than EMT tumors. When ultrasound was applied, both nanoaccumulation and apparent tumor permeability were increased in both settings. Notably, ultrasound effects differed with thermal and mechanical indices, such that increasing the thermal ultrasound dose increased nanoaccumulation in EMT tumors. Taken together, our results illustrate how ultrasound can be used to enhance nanoparticle accumulation in tumors by reducing their intratumoral pressure and increasing their vascular permeability. Cancer Res; 72(6); 1485–93. ©2012 AACR.