Dataset Information

Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery.

ABSTRACT: Cancer cell-specific diagnostic or therapeutic tools are commonly believed to significantly increase the success rate of cancer diagnosis and targeted therapies. To extend the repertoire of available cancer cell-specific phage fusion proteins and study their efficacy as navigating moieties, we used two landscape phage display libraries f8/8 and f8/9 displaying an 8- or 9-mer random peptide fusion to identify a panel of novel peptide families that are specific to Calu-3 cells. Using a phage capture assay, we showed that two of the selected phage clones, ANGRPSMT and VNGRAEAP (phage and their recombinant proteins are named by the sequence of the fusion peptide), are selective for the Calu-3 cell line in comparison to phenotypically normal lung epithelial cells and distribute into unique subcellular fractions.

SUBMITTER: Gillespie JW

PROVIDER: S-EPMC5066567 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery.

Gillespie James W JW Wei Lixia L Petrenko Valery A VA

Combinatorial chemistry & high throughput screening 20160101 5

Cancer cell-specific diagnostic or therapeutic tools are commonly believed to significantly increase the success rate of cancer diagnosis and targeted therapies. To extend the repertoire of available cancer cell-specific phage fusion proteins and study their efficacy as navigating moieties, we used two landscape phage display libraries f8/8 and f8/9 displaying an 8- or 9-mer random peptide fusion to identify a panel of novel peptide families that are specific to Calu-3 cells. Using a phage captu ...[more]

PMID: 27095536

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Project description:Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to other cell types in the placenta or to CSA-expressing cells in other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option.

Dataset Information

Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery.

Publications

Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery.

Similar Datasets

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