Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas

Nguyen, Juliane; Hossain, Shaolie S.; Cooke, Johann R. N.; Ellis, Jason A.; Deci, Michael B.; Emala, Charles W.; Bruce, Jeffrey N.; Bigio, Irving J.; Straubinger, Robert M.; Joshi, Shailendra

doi:10.1007/s11060-017-2429-5

Cited by 12 publications

(7 citation statements)

References 32 publications

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“…However, at low receptor levels (or in the absence of receptors), there was a decrease in targeting in the high velocity and high diffusion range. These results are consistent with a recent work of Nguyen et al [33], who have shown that nanoparticle uptake in a glioma is promoted under flowarrest condition (hyperfusion). Based on these results, the gain from the active targeting might be relatively high in the higher interstitial fluid velocity or diffusion ranges.…”

Section: Effects Of Particle Size Fluid Velocity and Particle Diffusionsupporting

confidence: 93%

A model-based analysis of tissue targeting efficacy of nanoparticles

Barua

2018

J. R. Soc. Interface.

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Tissue targeting is a critical challenge for systemic delivery of drug nanocarriers. To overcome this challenge, major research efforts have been undertaken to design ligand-conjugated nanoparticles. However, limited work has been done to quantitatively assess the effectiveness of such approach. In this work, using a mechanistic spatio-temporal model, I investigate the effectiveness of ligand-directed tissue targeting. By applying an approach from the colloidal filtration theory, I develop a Brownian dynamics model of nanoparticle-cell interaction. The model incorporates a single cell and its surrounding flow field. It considers both specific (receptor-mediated) and non-specific (bare cell surface-mediated) recognition of nanoparticles subject to convective and diffusive motion. Using the model, I investigate how the specific and non-specific interactions compare in determining the overall targeting efficacy. My analysis provides some interesting findings that contradict the general notion that effective targeting is possible based upon the differential receptor expression in cancer and non-cancer cells. I show that such strategy may yield only a marginal gain in the targeting efficacy. Moreover, non-specific interaction may have an important influence on particle recognition by cells even at high receptor expression levels.

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Section: Effects Of Particle Size Fluid Velocity and Particle Diffusionsupporting

confidence: 93%

A model-based analysis of tissue targeting efficacy of nanoparticles

Barua

2018

J. R. Soc. Interface.

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“…When combined with BBB disruption induced by focused ultrasound, intra-arterial liposome injection increases their deposition into tumor tissue of C6 tumor-bearing rats (158). Similarly, application of cationizable lipid micelles (163) with cationic short peptides such as the cell-penetrating trans-activator of transcription (TAT) was shown to increase the uptake of micelles (165) and can be used for selective drug delivery to gliomas. The translocation efficiency of nanoparticles is not only determined by surface charge.…”

Section: Bbb/btb Disruptionmentioning

confidence: 99%

“…The treatment effect was reported to last for more than 4 h (175). Furthermore, TCH is sufficient to enhance early regional deposition of nanoparticles such as micelles (163)(164)(165) and liposomes (158)(159)(160)(161)(162) into tumor tissues. This provides a novel approach for targeted intra-arterial tumor therapy ( Table 3).…”

Section: Tchmentioning

confidence: 99%

Strategies for Improved Intra-arterial Treatments Targeting Brain Tumors: a Systematic Review

2020

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Conventional treatments for brain tumors relying on surgery, radiation, and systemic chemotherapy are often associated with high recurrence and poor prognosis. In recent decades, intra-arterial administration of anti-cancer drugs has been considered a suitable alternative drug delivery route to intravenous and oral administration. Intra-arterial administration is believed to offer increasing drug responses by primary and metastatic brain tumors, and to be associated with better median overall survival. By directly injecting therapeutic agents into carotid or vertebral artery, intra-arterial administration rapidly increases intra-tumoral drug concentration but lowers systemic exposure. However, unexpected vascular or neural toxicity has questioned the therapeutic safety of intra-arterial drug administration and limits its widespread clinical application. Therefore, improving targeting and accuracy of intra-arterial administration has become a major research focus. This systematic review categorizes strategies for optimizing intra-arterial administration into five categories: (1) transient blood-brain barrier (BBB)/blood-tumor barrier (BTB) disruption, (2) regional cerebral hypoperfusion for peritumoral hemodynamic changes, (3) superselective endovascular intervention, (4) high-resolution imaging techniques, and (5) others such as cell and gene therapy. We summarize and discuss both preclinical and clinical research, focusing on advantages and disadvantages of different treatment strategies for a variety of cerebral tumor types.

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“…Plain and CCR2-targeting micelles were prepared as follows: mPEG-DSPE/NHS-PEG-DSPE/DiD (98/2/0.5) were dissolved in chloroform and mixed with the CCR2 antagonist dissolved in methanol. 14,18,19 The small molecule antagonist CCR2 was loaded into the lipid micelles at 1:22 molar ratio, which corresponds to a loading of 4.5% w/w. The solvent was removed by rotary evaporation to yield a lipid film.…”

Section: Micelle Synthesismentioning

confidence: 99%

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

Wang¹,

Seo²,

Deci³

et al. 2018

IJN

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BackgroundAfter myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.Materials and methodsHere, we developed poly(ethylene glycol) (PEG)-distearoylphos-phatidylethanolamine (PEG-DSPE) micelles loaded with a small molecule CCR2 antagonist to inhibit monocyte recruitment to the infarcted myocardium. To specifically target CCR2-expressing cells, PEG-DSPE micelles were further surface decorated with an anti-CCR2 antibody.ResultsTargeted PEG-DSPE micelles showed eight-fold greater binding to CCR2-expressing RAW 264.7 monocytes than plain, non-targeted PEG-DSPE micelles. In a mouse model of MI, CCR2-targeting PEG-DSPE micelles loaded with a CCR2 small molecule antagonist significantly decreased the number of Ly6Chigh inflammatory cells to 3% of total compared with PBS-treated controls. Furthermore, CCR2-targeting PEG-DSPE micelles significantly reduced the infarct size based on epicardial and endocardial infarct arc lengths.ConclusionBoth non-targeted and CCR2-targeting PEG-DSPE micelles showed a trend toward improving cardiac function. As such, PEG-DSPE micelles represent a promising cardiac therapeutic platform.

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Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas

Cited by 12 publications

References 32 publications

A model-based analysis of tissue targeting efficacy of nanoparticles

A model-based analysis of tissue targeting efficacy of nanoparticles

Strategies for Improved Intra-arterial Treatments Targeting Brain Tumors: a Systematic Review

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

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