Dataset Information

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.

ABSTRACT:

Purpose

Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.

Procedures

Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters.

Results

The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide.

Conclusions

Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.

SUBMITTER: Adochite RC

PROVIDER: S-EPMC6287260 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.

Adochite Ramona-Cosmina RC Moshnikova Anna A Golijanin Jovana J Andreev Oleg A OA Katenka Natallia V NV Reshetnyak Yana K YK

Molecular imaging and biology 20161001 5

<h4>Purpose</h4>Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.<h4>Procedures</h4>Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent d ...[more]

PMID: 27074841

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Project description:Chemically synthesized near-infrared aza-BODIPY dyes displayed off-on fluorescence at acidic pH (pKa = 6.2-6.6) through the suppression of the photoinduced electron transfer and/or internal charge transfer process. The apparent pKas of the dyes were shifted well above physiological pH in a hydrophobic microenvironment, which led to "turned-on" fluorescence in micelles and liposomes at neutral and basic pH. Bovine serum albumin also activated the fluorescence, though to a much lesser extent. When these small molecular dyes entered cells, instead of being fluorescent only in acidic organelles, the whole cytoplasm exhibited fluorescence, with a signal/background ratio as high as ?10 in no-wash live-cell imaging. The dye 1-labeled cells remained highly fluorescent even after 3 days. Moreover, slight variations of the dye structure resulted in significantly different intracellular fluorescence behaviors, possibly because of their different cellular uptake and intracellular activation capabilities. After the separation of cellular components, the fraction of plasma membrane and endoplasmic reticulum showed the highest fluorescence, further confirming the fluorescence activation by membrane structures. The fluorescence intensity of these dyes at different intracellular pHs (6.80 and 8.00) did not differ significantly, indicating that intracellular pH did not play a critical role. Altogether, we showed here for the first time that the fluorescence of pH-sensitive aza-BODIPY dyes was switched intracellularly not by acidic pH, but by intracellular membranes (and proteins as well). The excellent membrane permeability, ultrahigh fluorescence contrast ratio, persistent fluorescent signal, and minimal biological interference of dye 1 make it an ideal choice for live-cell imaging and in vivo cell tracking. These findings also imply that the intracellular fluorescence properties of pH-sensitive dyes should be carefully examined before they are used as pH indicators.

Dataset Information

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.

Purpose

Procedures

Results

Conclusions

Publications

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.

Similar Datasets

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