Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents

Bloch, Meital; Jablonowski, Lauren J.; Yavin, Eylon; Moradov, Dorit; Djavsarov, Irena; Nyska, Abraham; Wheatley, Margaret A.; Rubinstein, Abraham

doi:10.1016/j.ijpharm.2014.11.066

Cited by 7 publications

(16 citation statements)

References 42 publications

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“…[11,10,3] For this reason, the DoE analysis was conducted on the Flu-CPAA-100 (maximal cationic charge), while Flu-CPAA-20 (minimal cationic charge) served as a control polymer that represents a minimal cell-binding competency, yet baring a sufficient cationic charge necessary for the conjugation reaction with both IR-783-S-Ph-COOH fluorophore and the VRPMPLQ recognition peptide.…”

Section: Resultsmentioning

confidence: 99%

“…So were the experimental protocols of the in vitro (cell lines) and in vivo (colon mucosal tissues from DMH-induced rat model) uptake studies. [3] Cell lines…”

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

“…[3] Assessment of the specific binding properties of the fluorescentcationized polyacrylamide-peptide conjugate polymers in vitro…”

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

“…[3] The relation between increased charge density and extent of cell binding was measured in a preliminary study which included also Flu-CPAA-50 (containing 50 mol% of the cationic monomer).…”

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

“…The designated platform consists of a water-soluble cationized polyacrylamide (CPAA), with a marked affinity to sialic acid-rich mucinous tissues. [3] The CPAA was tagged with the near infrared (NIR) dye derivative IR-783-S-Ph-COOH to form Flu-CPAA. The recognition peptide VRPMPLQ, reported to bind to CRC tissues, [4] was conjugated to the Flu-CPAA backbone to form Flu-CPAA-Pep.…”

Section: Introductionmentioning

confidence: 99%

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A multifactorial analysis of complex pharmaceutical platforms: an application of design of experiments to targetable polyacrylamide and ultrasound contrast agents

Bloch

Kenett

Jablonowski

et al. 2015

Polymers for Advanced Techs

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To improve visualization of malignant regions in the colon epithelium during diagnostic procedures, we have recently suggested a multimodal system comprising the water-soluble cationized polyacrylamide, tagged with the near infrared dye derivative IR-783-S-Ph-COOH [fluorescent-cationized polyacrylamide (Flu-CPAA)] and conjugated to the recognition peptide VRPMPLQ to form Flu-CPAA-Pep. The fluorescent-cationized polyacrylamide-peptide conjugate (Flu-CPAA-Pep) is then incorporated into echogenic microbubbles (MBs) made of polylactic acid (PLA) to protect it from pre-mature interactions with plasma proteins upon intravenous administration. It is expected that under directed ultrasound interrogation the Flu-CPAA-Pep cargo would be released in the region of interest, as a result of the MBs rupture into submicron PLA fragments (SPF). Due to their nanoscale dimension, the SPF will escape from the vasculature and allow a specific binding of the Flu-CPAA-Pep to the suspected malignant tissue.The complex nature of the system requires a multifaceted statistically based experimental design. Here we apply a design of experiment methodology to enable effective screening of key parameters in our experimental setup. It enables the assessment of the role of the different formulation parameters by identifying statistically significant interactions as observed in vitro (cell lines) and in vivo (colon cancer-induced rat model). Particularly important was the identification of the interaction between the fraction (mol%) of the cationic monomer in the Flu-CPAA and (a) the presence of recognition peptide as assessed in the in vitro experiments and (b) the use of a presenting platform (whether MBs or SPF) as assessed in the in vivo experiments.

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Section: Resultsmentioning

confidence: 99%

“…So were the experimental protocols of the in vitro (cell lines) and in vivo (colon mucosal tissues from DMH-induced rat model) uptake studies. [3] Cell lines…”

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

“…[3] Assessment of the specific binding properties of the fluorescentcationized polyacrylamide-peptide conjugate polymers in vitro…”

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

Section: Fluorescent-cationized Polyacrylamide-peptide Conjugate Polymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A multifactorial analysis of complex pharmaceutical platforms: an application of design of experiments to targetable polyacrylamide and ultrasound contrast agents

Bloch

Kenett

Jablonowski

et al. 2015

Polymers for Advanced Techs

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Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration

et al. 2016

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The purpose of this study was to prepare tumor-specific dual-mode nanobubbles as both ultrasound contrast agents (UCAs) and near-infrared fluorescence (NIRF) imaging agents for female tumors. Recent studies have demonstrated the conjugation of anti-tumor ligands on the surface of nanobubbles for use as molecule-targeting ultrasound contrast agents for tumor visualization. However, this complicated procedure has also posed a challenge to nanobubble stability. Thus, in the present study, we combined the fluorescent dye, NIRF IR-780 iodide, which has lipid solubility and tumor-targeting characteristics, with the phospholipid film of nanobubbles that we constructed. We then characterized the physical features of the IR-780-nanobubbles, observed their tumor-targeting capacity in multiple female tumor cell types in vitro, and verified their capability for use in tumor-specific ultrasound contrast imaging and NIRF imaging in vivo. The results showed that the new IR-780-nanobubbles had a uniform nano-size (442.5 ± 48.6 nm) and stability and that they were safe and effective at NIRF imaging and ultrasound imaging in vitro. The IR-780-nanobubbles were found to automatically accumulate on different female tumor cells in vitro with a considerable targeting rate (close to 40 %) but did not accumulate on cardiac muscle cells used as a negative control. Importantly, the IR-780-nanobubbles can detect female tumors precisely via dual-mode imaging in vivo. In conclusion, the new dual-mode IR-780-nanobubbles are stable and have potential advantages in non-invasive tumor-specific detection for female tumors via contrast-enhanced ultrasound and NIRF imaging.

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Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment

David

2017

Advanced Drug Delivery Reviews

105

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Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents

Cited by 7 publications

References 42 publications

A multifactorial analysis of complex pharmaceutical platforms: an application of design of experiments to targetable polyacrylamide and ultrasound contrast agents

A multifactorial analysis of complex pharmaceutical platforms: an application of design of experiments to targetable polyacrylamide and ultrasound contrast agents

Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration

Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment

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