Optimizing the bioavailability of small molecular optical imaging probes by conjugation to an albumin affinity tag

Hahnenkamp, Anke; Alsibai, Wael; Bremer, Christoph; Höltke, Carsten

doi:10.1016/j.jconrel.2014.04.053

Cited by 15 publications

(23 citation statements)

References 39 publications

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“…One significant difference was the higher liver uptake of the Cy7 monomer. An alternative approach to slow clearance is to add an albumin binding peptide sequence through solid-phase synthesis [60], but increased liver uptake due to longer plasma exposure and/or scavenger uptake[75–76] and down-regulation of GLP-1R may not provide any targeting benefit over the more rapidly cleared monomer. In the pancreas, total uptake of 800CW and Cy7 monomers was not statistically different (p = 0.26).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Zhang

Thurber

2015

Mol Imaging Biol

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Purpose Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type-1 diabetes. The glucagon like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Procedures Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Results Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Conclusions Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, downregulation of the GLP-1 receptor and non-specific background uptake result in a higher TBR for fast-clearing agents.

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Section: Discussionmentioning

confidence: 99%

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Zhang

Thurber

2015

Mol Imaging Biol

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“…The albumin and drugs/peptide could bind together when there are strong interactions between them 169 . However, most drugs/peptide are unable to interact with albumin strongly, in which case the drugs/peptide could be conjugated with albumin-bound component 150 , 170 , 171 . The resulted prodrug/peptide-conjugate could form stable nanocomplex with albumin.…”

Section: Albumin As a Scaffold For Modification And Further Biomedicamentioning

confidence: 99%

“…Binding with albumin could considerably prolong the blood circulation time of small molecules. Thus, the conjugate of NIR cyanine dye and tumor-targeted ligand was bound to albumin through noncovalent interaction 171 . In vivo study demonstrated that the presence of albumin could enhance the biological half-life of the probe and help a large amount of the probe to reach the target site; these changes enabled the NIRF imaging of subcutaneous tumors for several days.…”

Section: Albumin As a Scaffold For Modification And Further Biomedicamentioning

confidence: 99%

Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

2017

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Biosafety is the primary concern in clinical translation of nanomedicine. As an intrinsic ingredient of human blood without immunogenicity and encouraged by its successful clinical application in Abraxane, albumin has been regarded as a promising material to produce nanoparticles for bioimaging and drug delivery. The strategies for synthesizing albumin-based nanoparticles could be generally categorized into five classes: template, nanocarrier, scaffold, stabilizer and albumin-polymer conjugate. This review introduces approaches utilizing albumin in the preparation of nanoparticles and thereby provides scientists with knowledge of goal-driven design on albumin-based nanomedicine.

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“…To obtain Cy5.5-labeled HSA and FITC-labeled PEG, HSA or PEG was agitated with Cy5.5-NHS or FITC for 8 hours away from light in the corresponding buffer solution. [31][32][33] The mixed solution was then dialyzed and lyophilized.…”

Section: Preparation Of Ptx-peg-hsa and Ptxhsa Nanosuspension Preparamentioning

confidence: 99%

A toxic organic solvent-free technology for the preparation of PEGylated paclitaxel nanosuspension based on human serum albumin for effective cancer therapy

Yin

Dong

Cui

et al. 2015

IJN

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Clinically, paclitaxel (PTX) is one of most commonly prescribed therapies against a wide range of solid neoplasms. Despite its success, the clinical applicability of PTX (Taxol ® ) is severely hampered by systemic toxicities induced by Cremophor EL. While attempts to bypass the need for Cremophor EL have been developed through platforms such as Abraxane™, nab™ relies heavily on the use of organic solvents, namely, chloroform. The toxicity introduced by residual chloroform poses a potential risk to patient health. To mitigate the toxicities of toxic organic solvent-based manufacture methods, we have designed a method for the formulation of PTX nanosuspensions (PTX-PEG [polyethylene glycol]-HSA [human serum albumin]) that eliminates the dependence on toxic organic solvents. Coined the solid-dispersion technology, this technique permits the dispersion of PTX into PEG skeleton without the use of organic solvents or Cremophor EL as a solubilizer. Once the PTX-PEG dispersion is complete, the dispersion can be formulated with HSA into nanosuspensions suitable for intravenous administration. Additionally, the incorporation of PEG permits the prolonged circulation through the steric stabilization effect. Finally, HSA-mediated targeting permits active receptor-mediated endocytosis for enhanced tumor uptake and reduced side effects. By eliminating the need for both Cremophor EL and organic solvents while simultaneously increasing antitumor efficacy, this method provides a superior alternative to currently accepted methods for PTX delivery.

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Optimizing the bioavailability of small molecular optical imaging probes by conjugation to an albumin affinity tag

Cited by 15 publications

References 39 publications

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

A toxic organic solvent-free technology for the preparation of PEGylated paclitaxel nanosuspension based on human serum albumin for effective cancer therapy

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Optimizing the bioavailability of small molecular optical imaging probes by conjugation to an albumin affinity tag

Cited by 15 publications

References 39 publications

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

A toxic organic solvent-free technology&nbsp;for&nbsp;the preparation of PEGylated paclitaxel&nbsp;nanosuspension based on human serum albumin for effective cancer therapy

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Product

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About

A toxic organic solvent-free technology for the preparation of PEGylated paclitaxel nanosuspension based on human serum albumin for effective cancer therapy