Targeted Delivery of Nanoparticles Bearing Fibroblast Growth Factor‐2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis

Chappell, John C.; Song, Ji Sun; Burke, Caitlin W.; Klibanov, Alexander L.; Price, Richard J.

doi:10.1002/smll.200800806

Cited by 87 publications

(76 citation statements)

References 41 publications

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“…We used a previously detailed FAL scheme6, 20, 21 that produces consistent arteriogenesis in the collateral arteries of the gracilis adductor muscles,6, 22, 23, 24, 25, 26, 27 along with minimal heterogeneity in the baseline collateral structure and known changes in flow direction from baseline. Male mice (10 to 12, 20 to 21, or 70 to 80 weeks of age for C57BL/6, Balb/c, and aged Balb/c studies, respectively) were anesthetized (intraperitoneal [IP] 120 mg/kg ketamine, 12 mg/kg xylazine, and 0.08 mg/kg atropine), depilated, and prepped for aseptic surgery.…”

Section: Methodsmentioning

confidence: 99%

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Heuslein

Gorick

Song

et al. 2017

JAHA

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BackgroundArteriogenesis is initiated by increased shear stress and is thought to continue until shear stress is returned to its original “set point.” However, the molecular mechanism(s) through which shear stress set point is established by endothelial cells (ECs) are largely unstudied. Here, we tested the hypothesis that DNA methyltransferase 1 (DNMT1)–dependent EC DNA methylation affects arteriogenic capacity via adjustments to shear stress set point.Methods and ResultsIn femoral artery ligation–operated C57BL/6 mice, collateral artery segments exposed to increased shear stress without a change in flow direction (ie, nonreversed flow) exhibited global DNA hypermethylation (increased 5‐methylcytosine staining intensity) and constrained arteriogenesis (30% less diameter growth) when compared with segments exposed to both an increase in shear stress and reversed‐flow direction. In vitro, ECs exposed to a flow waveform biomimetic of nonreversed collateral segments in vivo exhibited a 40% increase in DNMT1 expression, genome‐wide hypermethylation of gene promoters, and a DNMT1‐dependent 60% reduction in proarteriogenic monocyte adhesion compared with ECs exposed to a biomimetic reversed‐flow waveform. These results led us to test whether DNMT1 regulates arteriogenic capacity in vivo. In femoral artery ligation–operated mice, DNMT1 inhibition rescued arteriogenic capacity and returned shear stress back to its original set point in nonreversed collateral segments.ConclusionsIncreased shear stress without a change in flow direction initiates arteriogenic growth; however, it also elicits DNMT1‐dependent EC DNA hypermethylation. In turn, this diminishes mechanosensing, augments shear stress set point, and constrains the ultimate arteriogenic capacity of the vessel. This epigenetic effect could impact both endogenous collateralization and treatment of arterial occlusive diseases.

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Section: Methodsmentioning

confidence: 99%

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Heuslein

Gorick

Song

et al. 2017

JAHA

Self Cite

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“…For example, Chappell et al have reported that nanoparticles loaded with fibroblast growth factor-2 via ultrasonic destruction of microbubbles represent an effective and minimally invasive strategy for targeted stimulation of therapeutic arteriogenesis. 101 Further, Marin et al have used Pluronic micelles combined with pulsed ultrasound to enhance uptake of doxorubicin.…”

Section: Other Characteristics Of Urdds In Drug Deliverymentioning

confidence: 99%

Potential and problems in ultrasound-responsive drug delivery systems

Zhao¹,

Du²,

Lu³

et al. 2013

IJN

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Abstract:Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington's disease, thrombolysis, and disruption of the blood-brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future.

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“…10,11 Numerous animal models and tissues have shown that the destruction of circulating contrast agent microbubbles with local low-frequency ultrasound can obviously enhance the release of drug from the liposome in the ultrasonic sites. 12 In addition, ultrasound exposure alone had been proven to enhance the permeability of cell membrane, 13 and addition of microbubble has a significant potentiating effect.…”

Section: Introductionmentioning

confidence: 99%

Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy

Zhao

Zhang

Tian

et al. 2016

IJN

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Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/− UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes.

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Targeted Delivery of Nanoparticles Bearing Fibroblast Growth Factor‐2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis

Cited by 87 publications

References 41 publications

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Potential and problems in ultrasound-responsive drug delivery systems

Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy

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