Deep tissue penetration of nanoparticles using pulsed-high intensity focused ultrasound

Dong Gil You,Kwangmeyung Kim,Hong Yeol Yoon,Jae Hyung Park,Sangmin Jeon,Wooram Um,Sejin Son,Ick Chan Kwon

doi:10.1186/s40580-017-0124-z

Dong Gil You, Kwangmeyung Kim + Show 6 more

Open Access

https://doi.org/10.1186/s40580-017-0124-z

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Abstract

Recently, ultrasound (US)-based drug delivery strategies have received attention to improve enhanced permeation and retention (EPR) effect-based passive targeting efficiency of nanoparticles in vitro and in vivo conditions. Among the US treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have specialized for improving tissue penetration of various macromolecules and nanoparticles without irreversible tissue damages. In this study, we have demonstrated that pHIFU could be utilized to improve tissue penetration of fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-, 8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However, tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue damages, including the edema and chapped red blood cells. These overall results support that pHIFU treatment can enhance the extravasation and tissue penetration of FCNPs as well as induce irreversible tissue damages. We expect that our results can provide advantages to optimize pHIFU-mediated delivery strategy of nanoparticles for further clinical applications.

Highlights

Over the past several decades, nanotechnology based drug delivery platforms have emerged as an ‘All-in-one systems’ for diagnosis and therapy of diseases, including cancer
We have demonstrated that extracellular matrix (ECM) remodeling and disruption of the collagen matrix through pulsed-high intensity focused ultrasound (pHIFU) treatment for improving the deep tissue penetration and tumor targeting efficiency of nanoparticles [18]
PHIFU could enable the remodeling of ECM and destroy the collagen matrix, resulting in deep tissue penetration of nanoparticles, optimization of the pHIFU-mediated extravasation and tissue penetration of nanoparticles was not clear

Summary

Introduction

Over the past several decades, nanotechnology based drug delivery platforms have emerged as an ‘All-in-one systems’ for diagnosis and therapy of diseases, including cancer. Based on the enhanced permeability and retention (EPR) effect, nanoparticles could be accumulated by extravasation through leaky blood vessels in the angiogenesis-related diseases, such as infection, heart failure, renal disease and cancer [4, 5]. We have demonstrated that extracellular matrix (ECM) remodeling and disruption of the collagen matrix through pHIFU treatment for improving the deep tissue penetration and tumor targeting efficiency of nanoparticles [18]. 20 W/cm of pHIFU treatment did not occur acute tissue damage but increased blood flow, decreased collagen content, resulting in improving penetration and localization of nanoparticles into the tumor tissue. PHIFU could enable the remodeling of ECM and destroy the collagen matrix, resulting in deep tissue penetration of nanoparticles, optimization of the pHIFU-mediated extravasation and tissue penetration of nanoparticles was not clear

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