Dataset Information

Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.

ABSTRACT: meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 ?g of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT.

SUBMITTER: Abdelghany SM

PROVIDER: S-EPMC3582313 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.

Abdelghany Sharif M SM Schmid Daniela D Deacon Jill J Jaworski Jakub J Fay Francois F McLaughlin Kirsty M KM Gormley Julie A JA Burrows James F JF Longley Daniel B DB Donnelly Ryan F RF Scott Christopher J CJ

Biomacromolecules 20130131 2

meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. ...[more]

PMID: 23327610

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Project description:DNA methylation (DNAm) sensors are an emerging branch in the discipline of sensors. It is believed to be able to promote the next generation of epigenetics-based diagnostic technology. Differing from the traditional biochemical sensors that aimed at individual molecules, the challenge in DNAm sensors is how to determine the amount of 5-methylcytosine (5mC) in a continuous nucleotide sequence. Here, we report a comparative study about meso-tetra(4-carboxyphenyl)porphine (TCPP)-based DNAm sensing interfaces on a light-addressable potentiometric sensor (LAPS), depending on TCPP's postures that are flat in the π-conjugated TCPP layer on reduced-graphene-oxide-decorated LAPS (#1) and stand-up in the covalently anchored TCPP on glutaraldehyde (GA)-treated LAPS (#2), along with the blank one (only GA-treated LAPS, #3). These DNAm sensing interfaces are also distinct from the traditional biosensing interface on LAPS, that is: it is not functionalized by the sensing indicator (5mC antibody, in this case) but by the target nucleotide sequence. The surface characterization techniques such as Raman spectra, scanning electron microscopy, and X-ray photoelectron spectroscopy are conducted to prove the decorations, as well as the anchored nucleotides. It is found that, though all of them can detect as low as one 5mC in the target sequence, the enhanced DNAm sensitivity is obtained by #2, which is evidenced by the higher output-voltage changing ratio for the 5mC site of #2 than those of #1 and #3. Furthermore, the underlying causes for the improved sensitivity in #2 are proposed, according to the conformational and electronic properties of TCPP molecules. Conclusively, TCPP's synergetic function, including the molecular configuration and the activate (carboxyl) groups on its peripheral substituents, to improve the DNAm sensing interface on LAPS is investigated and demonstrated. This can shed light on a new approach for DNA methylation detection, with the merits of low cost, independence on bisulfite conversion, and polymerase chain reaction.

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Dataset Information

Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.

Publications

Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.

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