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

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 i...

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Bibliographic Details
Published in:Biomacromolecules 2013-02, Vol.14 (2), p.302-310
Main Authors: 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
Format: Article
Language:English
Subjects:
Alginates
Antibodies - immunology
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Applied sciences
Biological and medical sciences
Biological Transport
Caspase 8 - metabolism
Cell Line, Tumor
Chitosan - immunology
Colorectal Neoplasms - drug therapy
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
Exact sciences and technology
Glucuronic Acid - immunology
Hexuronic Acids - immunology
Humans
Medical sciences
Nanoparticles
Natural polymers
Pharmacology. Drug treatments
Photochemotherapy
Photosensitizing Agents - therapeutic use
Physicochemistry of polymers
Porphyrins - therapeutic use
Reactive Oxygen Species - metabolism
Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand - immunology
RNA Interference
RNA, Small Interfering
Starch and polysaccharides
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Summary: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.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm301858a