Enhanced Antitumor Activity of the Photosensitizer meso-Tetra(N-methyl-4-pyridyl) Porphine Tetra Tosylate through Encapsulation in Antibody-Targeted Chitosan/Alginate Nanoparticles

Sharif M Abdelghany, Daniela Schmid, Jill Deacon, Jakub Jaworski, Francois Fay, Kirsty M McLaughlin, Julie A Gormley, James F Burrows, Daniel B Longley, Ryan F Donnelly, Christopher J Scott

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 µg 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.
LanguageEnglish
Pages302-310
JournalBiomacromolecules
Volume14
Issue number2
Early online date17 Jan 2013
DOIs
Publication statusPublished - 11 Feb 2013

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Thymidine Monophosphate
Photosensitizing Agents
Photosensitizers
Alginate
Chitosan
Encapsulation
Antibodies
Nanoparticles
Photodynamic therapy
Cell death
Tumors
Hydrogels
TNF-Related Apoptosis-Inducing Ligand Receptors
Assays
Hydrogel
Cells
Pharmaceutical Preparations
Oxygen
porphine
alginic acid

Cite this

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title = "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 µg 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.",
author = "Abdelghany, {Sharif M} and Daniela Schmid and Jill Deacon and Jakub Jaworski and Francois Fay and McLaughlin, {Kirsty M} and Gormley, {Julie A} and Burrows, {James F} and Longley, {Daniel B} and Donnelly, {Ryan F} and Scott, {Christopher J}",
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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; Schmid, Daniela; Deacon, Jill; Jaworski, Jakub; Fay, Francois; McLaughlin, Kirsty M; Gormley, Julie A; Burrows, James F; Longley, Daniel B; Donnelly, Ryan F; Scott, Christopher J.

In: Biomacromolecules, Vol. 14, No. 2, 11.02.2013, p. 302-310.

Research output: Contribution to journalArticle

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AU - Schmid, Daniela

AU - Deacon, Jill

AU - Jaworski, Jakub

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AU - McLaughlin, Kirsty M

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AB - 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 µg 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.

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