Pulsed Focused Ultrasound Lowers Interstitial Fluid Pressure and Increases Nanoparticle Delivery and Penetration in Head and Neck Squamous Cell Carcinoma Xenograft Tumors

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dc.contributor.authorMohammadabadi, Ali
dc.contributor.authorHuynh, Ruby N
dc.contributor.authorWadajkar, Aniket S
dc.contributor.authorLapidus, Rena G
dc.contributor.authorKim, Anthony J
dc.contributor.authorRaub, Christopher B
dc.contributor.authorFrenkel, Victor
dc.date.accessioned2020-07-02T15:53:45Z
dc.date.available2020-07-02T15:53:45Z
dc.date.issued2020-06-19
dc.description.abstractNanocarriers offer a promising approach to significantly improve therapeutic delivery to solid tumors as well as limit the side effects associated with anti-cancer agents. However, their relatively large size can negatively affect their ability to efficiently penetrate into more interior tumor regions, ultimately reducing therapeutic efficacy. Poor penetration of large agents such as nanocarriers is attributed to factors in the tumor microenvironment such as elevated interstitial fluid pressure (IFP) and fibrillar collagen in the extracellular matrix. Our previous studies reported that pretreatment of solid tumor xenografts with nondestructive pulsed focused ultrasound (pFUS) can improve the delivery and subsequent therapy of a variety of therapeutic formulations in different tumor models, where the results were associated with expanded extracellular spaces (ECS), an increase in hydraulic conductivity, and decrease in tissue stiffness. Here, we demonstrate the inverse relationship between IFP and the penetration of systemically administered nanoparticle (NP) probes, where IFP increased from the tumor periphery to their center. Furthermore, we show that pretreatment with pFUS can safely reduce IFP and improve NP delivery; especially into the center of the tumors. These results coincide with effects generated in the fibrillar collagen network microstructure in the ECS as determined by quantitative polarized light microscopy. Whole tumor and histomorphometric analysis, however, did not show significant differences in collagen area fraction or collagen feature solidity, as well as tumor cross-sectional area and aspect ratio, as a result of the treatments. We present a biophysical model connecting the experimental results, where pFUS-mediated cytoarchitectural changes are associated with improved redistribution of the interstitial fluid and lower IFP. The resulting improvement in NP delivery supports our previous therapeutic studies and may have implications for clinical applications to improve therapeutic outcomes in cancer therapy.en_US
dc.description.sponsorshipThis research was supported in part by the National Institutes of Health (R37 CA218617) and a University of Maryland Greenbaum Comprehensive Cancer Center Pilot Award, University of Maryland School of Medicine. We would like to thank Dr. Ru-Ching Hsia for her assistance with processing the tumor samples for fluorescence microscopy, and Dr. Tanu Sharma for assistance with tumor processing for light microscopy. We would also like to thank the Genomics Core at UMGCCC for validating the FaDu cells.en_US
dc.description.urihttps://iopscience.iop.org/article/10.1088/1361-6560/ab9705/pdfen_US
dc.format.extent15 pagesen_US
dc.genrejournal articles postprintsen_US
dc.identifierdoi:10.13016/m2zmen-vsoy
dc.identifier.citationAli Mohammadabadi et al., Pulsed focused ultrasound lowers interstitial fluid pressure and increases nanoparticle delivery and penetration in head and neck squamous cell carcinoma xenograft tumors, Physics in Medicine & Biology, Volume 65, Number 12, https://doi.org/10.1088/1361-6560/ab9705en_US
dc.identifier.urihttps://doi.org/10.1088/1361-6560/ab9705
dc.identifier.urihttp://hdl.handle.net/11603/19055
dc.language.isoen_USen_US
dc.publisherIOPen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Mechanical Engineering Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)*
dc.rightsAccess to this item will begin on 7/30/21
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/*
dc.titlePulsed Focused Ultrasound Lowers Interstitial Fluid Pressure and Increases Nanoparticle Delivery and Penetration in Head and Neck Squamous Cell Carcinoma Xenograft Tumorsen_US
dc.typeTexten_US

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