Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles

Fokong, Stanley; Theek, Benjamin; Wu, Zhuojun; Koczera, Patrick; Appold, Lia; Jorge, Samuel Monteiro; Resch‐Genger, Ute; Zandvoort, Marc van; Storm, Gert; Kießling, Fabian; Lammers, Twan

doi:10.1016/j.jconrel.2012.05.007

Cited by 137 publications

(117 citation statements)

References 45 publications

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“…Microbubbles can release its payload at specific position, in which the drug vehicle receives US energy. [4][5][6][7] The interactions between microbubbles and US can increase the permeability of particularly in terms of high drug-loading, sustained release action, and targeted lymphatic absorption. 15 16 The potential advantages of both microbubbles and nanoparticles motivated this research to develop a new drug delivery vehicle.…”

Section: Introductionmentioning

confidence: 99%

A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles

Wang¹,

Li²,

Tian³

et al. 2016

j biomed nanotechnol

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Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis.

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Section: Introductionmentioning

confidence: 99%

A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles

Wang¹,

Li²,

Tian³

et al. 2016

j biomed nanotechnol

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“…EGFR or PSMA), or by tumor endothelial cells (e.g. VEGFR2 or integrins) 11,[19][20][21][22][23] .In the last decade, a significant number of drug targeting studies have focused on the synthesis and evaluation of actively targeted nanomedicines, primarily aiming to deliver higher payloads of drugs to tumors over time. [24][25][26][27][28][29][30][31] .…”

mentioning

confidence: 99%

Passive versus Active Tumor Targeting Using RGD- and NGR-Modified Polymeric Nanomedicines

et al. 2014

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Enhanced permeability and retention (EPR), and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and RGD-and NGR-based active tumor targeting have received considerable attention in the last couple of years. Using several different in vivo and ex vivo optical imaging techniques, we here visualized and quantified the benefit of RGD-and NGR-based vascular vs. EPR-mediated passive tumor targeting. This was done using ~10 nm-sized polymeric nanocarriers, which were either labeled with DY-676 (peptide-modified polymers) or with DY-750 (peptide-free polymers). Upon co-injection into mice bearing both highly leaky CT26 and poorly leaky BxPC3 tumors, it was found that vascular targeting did work, resulting in rapid and efficient early binding to tumor blood vessels, but that over time, passive targeting was significantly more efficient, leading to higher overall levels and to more efficient retention within tumors. Although this situation might be different for larger carrier materials, these insights indicate that caution should be taken not to over-estimate the potential of active over passive tumor targeting. KeywordsNanomedicine; Drug targeting; EPR; RGD; NGR Paralleled by the ever-increasing advances in nanotechnology and chemical engineering, nanomedicine formulations have started to attract significant attention in the last couple of years. Nanomedicines are 1-100(0) nm-sized carrier materials designed to improve the biodistribution and target site accumulation of low-molecular-weight (chemo-) therapeutic agents. By means of both passive and active targeting mechanisms, nanocarrier materials * Corresponding Authors Prof. Dr. Fabian Kiessling; Tel: +49-241-8080116; fkiessling@ukaachen.de Dr. Dr. Twan Lammers; Tel: +49-241-8036681; tlammers@ukaachen.de. Supporting Information Materials and methods describing the synthesis and characterization of the polymeric nanocarriers are provided as supplementary information. This material is available free of charge via the Internet at http://pubs.acs.org. Europe PMC Funders GroupAuthor Manuscript Nano Lett. Author manuscript; available in PMC 2014 March 04. Published in final edited form as:Nano Lett. 2014 February 12; 14(2): 972-981. doi:10.1021/nl404391r. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts aim to more efficiently deliver drug molecules to pathological sites, while at the same time preventing their accumulation in potentially endangered healthy tissues, thereby beneficially affecting the balance between their efficacy and toxicity 1-4 .Passive drug targeting relies on the hyper-permeable tumor vasculature. Endothelial gaps and improperly aligned vascular endothelium result in leaky blood vessels, which enable the extravasation of carrier materials with sizes of up to several 100's of nm into the tumor interstitium. In addition to this, dysfunctional lymphatic drainage results in the retention of extravasated nanomaterials within tumo...

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“…The concept of hyperthermia-triggered drug delivery using TSLs, as proposed by Yatvin and Weinstein [195], has been evaluated in preclinical models with various heat sources, such as needle-based radiofrequency (RF), water baths, light sources, and catheters [196][197][198][199]. Recently, multiple preclinical studies have been published showing HIFU-induced drug delivery in mice, rats and rabbits [172,174,200,201]. The challenge of establishing and maintaining hyperthermia, as well as of monitoring the temperature non-invasively, strongly hampered the clinical translation of temperature-triggered drug delivery.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

Mangraviti¹,

Gullotti²,

Tyler³

et al. 2016

Journal of Controlled Release

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Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles

Cited by 137 publications

References 45 publications

A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles

A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles

Passive versus Active Tumor Targeting Using RGD- and NGR-Modified Polymeric Nanomedicines

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

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