Journal article
Manipulating multifaceted microbubble shell composition to target both TRAIL-sensitive and resistant cells
Journal of biomedical materials research. Part A, v 106(7), pp 1903-1915
01 Jul 2018
PMID: 29521001
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
This study represents the first attempt to combine surface TRAIL expression and doxorubicin co-encapsulation in a single drug delivery agent in the form of ultrasound-responsive microbubbles that shatter into fragments, or nanoshards, in an ultrasound beam. We compare customized microbubbles of different polymeric shell compositions, and investigate the effect of both shell composition and incorporation of doxorubicin on action against TRAIL-sensitive MDA-MB-231 and TRAIL-resistant MCF7 human breast adenocarcinoma cells. Ligation of TRAIL only significantly impacted MDA-MB-231 cells predominantly by apoptosis, and had minimal effect on MCF12A (normal control) cells. For all shell types, nanoshards had a greater effect (apoptotic death ranging from approximately 25% for 1 wt % LipidPEG to 50% for 100% PLA), reflecting the greater surface area and larger number of particles that ultrasound generates. Encapsulation of doxorubicin generated necrosis in all cell lines, but PEGylation produced less effective necrosis in all cell lines. Co-encapsulation of doxorubicin within the contrast agent shell increased MDA-MB-231 cell death to approximately 40-80%, representing a marked increase over TRAIL alone, reflecting the dramatic effect of shell composition. Additionally, shells that co-encapsulated TRAIL and doxorubicin resulted in approximately 30-60% death in TRAIL-resistant MCF7 human breast adenocarcinoma cells, compared with little apoptotic response in these cells from shells encapsulating TRAIL alone, demonstrating the sensitization effect of the drug. This work has resulted in production of a library of effective ultrasound-triggered, minimally immunogenic, targeted drug delivery agents for potential use in cancer therapy, and represents a promising multifaceted treatment to better serve the population with solid tumors. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1903-1915, 2018.
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Details
- Title
- Manipulating multifaceted microbubble shell composition to target both TRAIL-sensitive and resistant cells
- Creators
- Lauren J. Jablonowski - Drexel UniversityDolores Conover - Drexel UniversityNutte T. Teraphongphom - Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, 3141 Chestnut St, Philadelphia, PA 19104 USAMargaret A. Wheatley - Drexel University
- Publication Details
- Journal of biomedical materials research. Part A, v 106(7), pp 1903-1915
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- Society of Interventional Radiology W. W. Smith Charitable Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000434124100014
- Scopus ID
- 2-s2.0-85044730530
- Other Identifier
- 991019169640404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials