Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model

Zhang, Hua; Kusunose, Jiro; Kheirolomoom, Azadeh; Seo, Jai Woong; Qi, Jinyi; Watson, Katherine D.; Lindfors, Heather A.; Ruoslahti, Erkki; Sutcliffe, Julie L.; Ferrara, Katherine W.

doi:10.1016/j.biomaterials.2007.12.033

Cited by 39 publications

(53 citation statements)

References 25 publications

(38 reference statements)

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“…Recently, phage display technique was used to explore homing peptides for targeted repair [15][16][17]. A series of ischemic myocardium-targeted peptides were identified that could provide a tool for VEGF delivery [18][19][20][21]. However, the definite mechanism through which the…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Yang

Shi

Hou

et al. 2015

Journal of Controlled Release

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Section: Accepted Manuscriptmentioning

confidence: 99%

Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Yang

Shi

Hou

et al. 2015

Journal of Controlled Release

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“…Creation of a clinically-optimized ultrasound-enhanced drug or gene delivery vehicle is challenging due to the vast parameter space of potential materials, targeting ligands, cargos, and ultrasound parameters. We and others are developing cross-modality imaging methods in which nuclear medicine, magnetic resonance imaging, and optical imaging probes are used to visualize the delivery vehicle or the model drug [51][52][53][54].The great strength of nuclear imaging techniques, particularly positron emission tomography, is the real-time and highly sensitive full-body pharmacokinetics currently possible in pre-clinical studies [54,55]. Magnetic resonance imaging (MRI) techniques can be used to visualize the biodistribution of drugs or vehicles [52] and the activation of delivery vehicles in limited cases [51], and MRI can also be used to monitor local temperature in pre-clinical and clinical studies [56].…”

Section: Other Issuesmentioning

confidence: 99%

Driving delivery vehicles with ultrasound

Ferrara

2008

Advanced Drug Delivery Reviews

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225

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Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. KeywordsUltrasound; Therapy; Drug delivery; Gene delivery; Sonoporation; Cavitation As an imaging modality, ultrasound is widely employed and valued for its real time applications, low cost, simplicity, and safety. Waves of alternating increased and decreased pressure propagate from the transducer, typically resulting in a maximum intensity in a focal region chosen by the operator. The dimensions of the focal region can vary from tens of microns for high frequency ultrasound to centimeters for an unfocused therapeutic beam. Most clinical instruments are engineered to effectively image from the body surface to 24 or more centimeters in depth. The ability to locally control and maximize energy deposition deep within the body facilitates a broad range of clinical opportunities for ultrasound imaging and therapy. Developing over four decades, clinical and commercial application of ultrasonic therapies spans hyperthermia, drug delivery, lipoplasty, and thrombolysis [1,2]. A complete and precise summary of the potential applications for ultrasonic enhancement of drug and gene delivery remains challenging as the mechanisms are multiple and not fully characterized. From an engineering viewpoint, the methods by which ultrasound facilitates drug and gene delivery can be summarized as direct changes in the biological or physiological properties of tissues facilitating transport, direct changes in the drug or vehicle increasing bioavailability or enhancing efficacy, and indirect effects by which ultrasound acts on the vehicle to produce changes in the surrounding tissue. While there are common mechanisms between these methods, the engineering challenges associated with the optimization of ultrasound systems and drug and vehicle design are unique for each method. Promising examples of each of these methods can be identified at this time and are addressed below.☆ This commentary is part of the Advanced Drug Delivery Reviews theme issue on "Ultrasound in Drug and Gene Delivery".

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“…The F3 peptide, F3 LPP and scrambled F3 LPPs were synthesized as in [50] and described briefly below. The reagents, including solvents, amino acids, Fmoc-Peg27-OH, and Fmoc-Peg4-OH, were obtained from EMD Biosciences (La Jolla, CA) unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

et al. 2017

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Nucleolin (NCL) plays an important role in tumor vascular development. An increased endothelial expression level of NCL has been related to cancer aggressiveness and prognosis and has been detected clinically in advanced tumors. Here, with a peptide targeted to NCL (F3 peptide), we created an NCL-targeted microbubble (MB) and compared the performance of F3-conjugated MBs with non-targeted (NT) MBs both in vitro and in vivo. In an in vitro study, F3-conjugated MBs bound 433 times more than NT MBs to an NCL-expressing cell line, while pretreating cells with 0.5 mM free F3 peptide reduced the binding of F3-conjugated MBs by 84%, n=4, p<0.001. We then set out to create a method to extract both the tumor wash-in and wash-out kinetics and tumor accumulation following a single injection of targeted MBs. In order to accomplish this, a series of ultrasound frames (a clip) was recorded at the time of injection and subsequent time points. Each pixel within this clip was analyzed for the minimum intensity projection (MinIP) and average intensity projection (AvgIP). We found that the MinIP robustly demonstrates enhanced accumulation of F3-conjugated MBs over the range of tumor diameters evaluated here (2 to 8 mm), and the difference between the AvgIP and the MinIP quantifies inflow and kinetics. The inflow and clearance were similar for unbound F3-conjugated MBs, control (non-targeted) and scrambled control agents. Targeted agent accumulation was confirmed by a high amplitude pulse and by a two-dimensional Fourier Transform technique. In summary, F3-conjugated MBs provide a new imaging agent for ultrasound molecular imaging of cancer vasculature, and we have validated metrics to assess performance using low mechanical index strategies that have potential for use in human molecular imaging studies.

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Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model

Cited by 39 publications

References 25 publications

Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction

Driving delivery vehicles with ultrasound

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

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