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CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells.

ABSTRACT: CD44v6 peptide functionalized nanoparticles are fabricated in a facile and controllable way to selectively bind to CD44v6 positive tumor cells with highly efficient anticancer and antimetastatic properties. The reported modular synthesis and facile preparation makes this system highly potent for developing novel multifunctional nanocarriers for therapeutic and/or diagnostic anticancer applications.

SUBMITTER: Li L

PROVIDER: S-EPMC5238741 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells.

Li Linxian L Schmitt Mark M Matzke-Ogi Alexandra A Wadhwani Parvesh P Orian-Rousseau Veronique V Levkin Pavel A PA

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20161220 1

<b>CD44v6 peptide functionalized nanoparticles</b> are fabricated in a facile and controllable way to selectively bind to CD44v6 positive tumor cells with highly efficient anticancer and antimetastatic properties. The reported modular synthesis and facile preparation makes this system highly potent for developing novel multifunctional nanocarriers for therapeutic and/or diagnostic anticancer applications. ...[more]

PMID: 28105395

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Project description:One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is the ability to ensure that the nanosystems enter those cells. Here, we use 2 nm (metal core) gold nanoparticles to target human hepatocellular carcinoma (HepG2) cells stably transfected with the SERPINB3 (SB3) protein. The nanoparticles were coated with a 85:15 mixture of thiols featuring, respectively, a phosphoryl choline (to ensure water solubility and biocompatibility) and a 28-mer peptide corresponding to the amino acid sequence 21-47 of the hepatitis B virus-PreS1 protein (PreS1(21-47)). Conjugation of the peptide was performed via the maleimide-thiol reaction in methanol, allowing the use of a limited amount of the targeting molecule. This is an efficient procedure also in the perspective of selecting libraries of new targeting agents. The rationale behind the selection of the peptide is that SB3, which is undetectable in normal hepatocytes, is overexpressed in hepatocellular carcinoma and in hepatoblastoma and has been proposed as a target of the hepatitis B virus (HBV). For the latter, the key recognition element is the PreS1(21-47) peptide, which is a fragment of one of the proteins composing the viral envelope. The ability of the conjugated nanoparticles to bind the target protein SB3, expressed in liver cancer cells, was investigated by surface plasmon resonance analysis and in vitro via cellular uptake analysis followed by atomic absorption analysis of digested samples. The results showed that the PreS1(21-47) peptide is a suitable targeting agent for cells overexpressing the SB3 protein. Even more important is the evidence that the gold nanoparticles are internalized by the cells. The comparison between the surface plasmon resonance analysis and the cellular uptake studies suggests that the presentation of the protein on the cell surface is critical for efficient recognition.

Dataset Information

CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells.

Publications

CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells.

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