Ultrasound Increases Nanoparticle Delivery by Reducing Intratumoral Pressure and Increasing Transport in Epithelial and Epithelial-mesenchymal Transition Tumors

Overview

Journal Cancer Res

Specialty Oncology

Date 2012 Jan 28

PMID 22282664

Citations 44

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Engineering Versatile Nanomedicines for Ultrasonic Tumor Immunotherapy.

Liang J, Qiao X, Qiu L, Xu H, Xiang H, Ding H Adv Sci (Weinh). 2023; 11(3):e2305392.

PMID: 38041509 PMC: 10797440. DOI: 10.1002/advs.202305392.

Solid tumor treatment via augmentation of bioactive C6 ceramide levels with thermally ablative focused ultrasound.

Thim E, Fox T, Deering T, Vass L, Sheybani N, Kester M Drug Deliv Transl Res. 2023; 13(12):3145-3153.

PMID: 37335416 PMC: 11423265. DOI: 10.1007/s13346-023-01377-w.

Solid Tumor Treatment via Augmentation of Bioactive C6 Ceramide Levels with Thermally Ablative Focused Ultrasound.

Thim E, Fox T, Deering T, Vass L, Sheybani N, Kester M bioRxiv. 2023; .

PMID: 36993445 PMC: 10055354. DOI: 10.1101/2023.03.23.532394.

Large-Volume Focused-Ultrasound Mild Hyperthermia for Improving Blood-Brain Tumor Barrier Permeability Application.

Chan H, Chang H, Lin W, Chen G Pharmaceutics. 2022; 14(10).

PMID: 36297445 PMC: 9610093. DOI: 10.3390/pharmaceutics14102012.

Ultrasound-Targeted Microbubble Destruction: Modulation in the Tumor Microenvironment and Application in Tumor Immunotherapy.

Han Y, Sun J, Wei H, Hao J, Liu W, Wang X Front Immunol. 2022; 13:937344.

PMID: 35844515 PMC: 9283646. DOI: 10.3389/fimmu.2022.937344.

References

Wu F, Wang Z, Lu P, Xu Z, Chen W, Zhu H . Activated anti-tumor immunity in cancer patients after high intensity focused ultrasound ablation. Ultrasound Med Biol. 2004; 30(9):1217-22. DOI: 10.1016/j.ultrasmedbio.2004.08.003. View

Seo J, Zhang H, Kukis D, Meares C, Ferrara K . A novel method to label preformed liposomes with 64Cu for positron emission tomography (PET) imaging. Bioconjug Chem. 2008; 19(12):2577-84. PMC: 2756669. DOI: 10.1021/bc8002937. View

Rygh C, Qin S, Seo J, Mahakian L, Zhang H, Adamson R . Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET. Clin Cancer Res. 2010; 17(3):550-9. PMC: 3107124. DOI: 10.1158/1078-0432.CCR-10-2049. View

Dreher M, Liu W, Michelich C, Dewhirst M, Yuan F, Chilkoti A . Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006; 98(5):335-44. DOI: 10.1093/jnci/djj070. View

Lin Y, Samardzic H, Adamson R, Renkin E, Clark J, Reed R . Phosphodiesterase 4 inhibition attenuates atrial natriuretic peptide-induced vascular hyperpermeability and loss of plasma volume. J Physiol. 2010; 589(Pt 2):341-53. PMC: 3043537. DOI: 10.1113/jphysiol.2010.199588. View

Sharma G, Anabousi S, Ehrhardt C, Kumar M . Liposomes as targeted drug delivery systems in the treatment of breast cancer. J Drug Target. 2006; 14(5):301-10. DOI: 10.1080/10611860600809112. View

Coulombe P, Wong P . Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat Cell Biol. 2004; 6(8):699-706. DOI: 10.1038/ncb0804-699. View

Ahmed M, Monsky W, Girnun G, Lukyanov A, DIppolito G, Kruskal J . Radiofrequency thermal ablation sharply increases intratumoral liposomal doxorubicin accumulation and tumor coagulation. Cancer Res. 2003; 63(19):6327-33. View

Miller M, Miller D, Brayman A . A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective. Ultrasound Med Biol. 1996; 22(9):1131-54. DOI: 10.1016/s0301-5629(96)00089-0. View

10.

Maeda H . The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001; 41:189-207. DOI: 10.1016/s0065-2571(00)00013-3. View

11.

Hu Z, Yang X, Liu Y, Morse M, Lyerly H, Clay T . Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs. Biochem Biophys Res Commun. 2005; 335(1):124-31. PMC: 1974850. DOI: 10.1016/j.bbrc.2005.07.071. View

12.

Locke J, Zeug A, Thompson Jr D, Allan J, Mazzarella K, Novak P . Localized versus regional hyperthermia: comparison of xenotransplants treated with a small animal ultrasound system and waterbath limb immersion. Int J Hyperthermia. 2005; 21(3):271-81. DOI: 10.1080/02656730500070151. View

13.

Krasovitski B, Frenkel V, Shoham S, Kimmel E . Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects. Proc Natl Acad Sci U S A. 2011; 108(8):3258-63. PMC: 3044354. DOI: 10.1073/pnas.1015771108. View

14.

Douezan S, Guevorkian K, Naouar R, Dufour S, Cuvelier D, Brochard-Wyart F . Spreading dynamics and wetting transition of cellular aggregates. Proc Natl Acad Sci U S A. 2011; 108(18):7315-20. PMC: 3088609. DOI: 10.1073/pnas.1018057108. View

15.

Chanson L, Brownfield D, Garbe J, Kuhn I, Stampfer M, Bissell M . Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells. Proc Natl Acad Sci U S A. 2011; 108(8):3264-9. PMC: 3044373. DOI: 10.1073/pnas.1019556108. View

16.

Krol A, Dewhirst M, Yuan F . Effects of cell damage and glycosaminoglycan degradation on available extravascular space of different dextrans in a rat fibrosarcoma. Int J Hyperthermia. 2003; 19(2):154-64. DOI: 10.1080/02656730210166519. View

17.

Schafer M, Werner S . Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 2008; 9(8):628-38. DOI: 10.1038/nrm2455. View

18.

Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H . Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002; 3(8):487-97. DOI: 10.1016/s1470-2045(02)00818-5. View

19.

Kong G, Braun R, Dewhirst M . Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature. Cancer Res. 2001; 61(7):3027-32. View

20.

Tang D, Khaleque M, Jones E, Theriault J, Li C, Wong W . Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones. 2005; 10(1):46-58. PMC: 1074571. DOI: 10.1379/csc-44r.1. View