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Increasing the density of nanomedicines improves their ultrasound-mediated delivery to tumours
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SYSNO ASEP 0444229 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Increasing the density of nanomedicines improves their ultrasound-mediated delivery to tumours Author(s) Mo, S. (GB)
Carlisle, R. (GB)
Laga, Richard (UMCH-V) RID, ORCID
Myers, R. (GB)
Graham, S. (GB)
Cawood, R. (GB)
Ulbrich, Karel (UMCH-V) RID
Seymour, L. (GB)
Coussios, C. C. (GB)Source Title Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 210, 28 July (2015), s. 10-18Number of pages 9 s. Language eng - English Country NL - Netherlands Keywords delivery ; density ; tumour Subject RIV CE - Biochemistry R&D Projects EE2.3.30.0029 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMCH-V - RVO:61389013 UT WOS 000356238700002 EID SCOPUS 84929611293 DOI 10.1016/j.jconrel.2015.05.265 Annotation Nanomedicines have provided fresh impetus in the fight against cancer due to their selectivity and power. However, these agents are limited when delivered intravenously due to their rapid clearance from the bloodstream and poor passage from the bloodstream into target tumours. Here we describe a novel stealthing strategy which addresses both these limitations and thereby demonstrate that both the passive and mechanically-mediated tumour accumulation of the model nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold nanoparticles were thoroughly modified with 2 kDa polyethyleneglycol (PEG) and then linked to Ad via a single reduction-cleavable 5 kDa PEG. The resulting Ad–gold–PEG construct was compared to non-modified Ad or conventionally stealthed Ad–poly[N-(2-hydroxypropyl)methacrylamide] (Ad–PHPMA). Notably, although Ad–gold–PEG was of similar size and surface charge to Ad–PHPMA the increase in density, resulting from the inclusion of the gold nanoparticles, provided a substantial enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking phantom, the level and distance of Ad–gold–PEG transport was shown to be substantially greater than achieved with Ad–PHPMA. In in vivo studies 0.1% of an unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the injected dose was recovered from the tumours of mice treated with Ad–gold–PEG and ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted from this strategy. This stealthing and density-increasing technology could ultimately enhance clinical utility of intravenously delivered nanoscale medicines including viruses, liposomes and antibodies. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2016
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