Gd‐DTPA‐loaded PLGA microbubbles as both ultrasound contrast agent and MRI contrast agent—A feasibility research

Meng, Aimin; Wang, Zhigang; Ran, Haitao; Guo, Dajing; Yu, Jinhong; Li, Ao; Chen, Weijuan; Wu, Wei; Zheng, Yuanyi

doi:10.1002/jbm.b.31614

Cited by 53 publications

(42 citation statements)

References 26 publications

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“…In addition, gene delivery has been demonstrated in vitro and in vivo , while simultaneously allowing molecular imaging of the polymersome [74,78,79]. Gd-DTPA and iron-oxide loaded PLGA nanoparticles have been used with US and MRI [80,81]. Recently, a construct with similar efficacy and rapid clearance was reported to limit toxicity [82].…”

Section: Nanoparticlesmentioning

confidence: 99%

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Imaging and drug delivery using theranostic nanoparticles

Janib

Moses

MacKay

2010

Advanced Drug Delivery Reviews

1,106

766

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Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core–shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents.

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Section: Nanoparticlesmentioning

confidence: 99%

“…Despite the advantages already mentioned, these core–shell nanoparticles suffer from some inherent shortcomings such as toxicity, rapid clearance, and poor biodistribution and biodegradation. Various strategies are in development to circumvent these problems [80,81]. …”

Section: Nanoparticlesmentioning

confidence: 99%

Imaging and drug delivery using theranostic nanoparticles

Janib

Moses

MacKay

2010

Advanced Drug Delivery Reviews

1,106

766

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“…Gd(III) enhances the positive contrast of blood by shortening both the longitudinal and transverse proton relaxation times, T 1 and T 2 [20–22]. Previously, Gd(III)-DTPA was loaded into the shell of 1.5-μm diameter polymeric microbubbles [23]. The enhancement of the T 1 -weighted MRI signal was reportedly a linear function of Gd(III)-DTPA-loaded microbubble concentration.…”

Section: Introductionmentioning

confidence: 99%

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery

et al. 2012

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We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 105 ± 3.0 × 105 Gd(III)/μm2 after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r1) and transverse (r2) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM−1s−1, respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants.

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“…Gd-DTPA loaded microbubbles of PLGA were designed as multimodal contrast agents for both US and MRI [17]. Albumin-based microbubbles filled with decafluorobutane gas and containing Gd-DTPA covalently linked to Human Serum Allbumin (HSA) were used to enhance the detection of inflamed sites within the vascular wall [18].…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents

Cavalli

Argenziano

Vigna

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Please cite this article as: R. Cavalli, M. Argenziano, E. Vigna, P. Giustetto, E. Torres, S. Aime, E. Terreno, Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents, Colloids and Surfaces B: Biointerfaces (2015), http://dx.doi.org/10. 1016/j.colsurfb.2015.03.023 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 27 A c c e p t e d M a n u s c r i p A c c e p t e d M a n u s c r i p t 2 ABSTRACT Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro-and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd (III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500 nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro. The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37 °C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles.In summary, chitosan drug-loaded nanobubbles with Gd (III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anticancer treatments.

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Gd‐DTPA‐loaded PLGA microbubbles as both ultrasound contrast agent and MRI contrast agent—A feasibility research

Abstract: Gd-DTPA-loaded PLGA microbubbles could enhance both ultrasound imaging and MRI imaging.

Cited by 53 publications

References 26 publications

Imaging and drug delivery using theranostic nanoparticles

Imaging and drug delivery using theranostic nanoparticles

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents

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