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.
authors: School of Pharmacy, Centre for Cancer Research and Cell Biology, Queen's University Belfast , 97 Lisburn Road, Belfast, United Kingdom.
authors: Sharif M
authors: SM
authors: Abdelghany
authors: Daniela
authors: D
authors: Schmid
authors: Jill
authors: J
authors: Deacon
authors: Jakub
authors: J
authors: Jaworski
authors: Francois
authors: F
authors: Fay
authors: Kirsty M
authors: KM
authors: McLaughlin
authors: Julie A
authors: JA
authors: Gormley
authors: James F
authors: JF
authors: Burrows
authors: Daniel B
authors: DB
authors: Longley
authors: Ryan F
authors: RF
authors: Donnelly
authors: Christopher J
authors: CJ
authors: Scott
mesh_terms: D000464:Alginates; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001692:Biological Transport; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000276:immunology; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D020723:Glucuronic Acid / Q000276:immunology; D006603:Hexuronic Acids / Q000276:immunology; D006801:Humans; D053758:Nanoparticles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology
chemical_list: D000464:Alginates; D000906:Antibodies; D000970:Antineoplastic Agents; D006603:Hexuronic Acids; D017319:Photosensitizing Agents; D011166:Porphyrins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C021096:tetra(4-N-methylpyridyl)porphine; D020723:Glucuronic Acid; D048271:Chitosan; D053181:Caspase 8