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

• Published in: Biomacromolecules Vol. 14; no. 2; pp. 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: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 11-02-2013
• 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; Surface reaction; Photodynamic therapy; Targeting; Antibody; Control release polymer; Gelation; Porphin; Drug carrier; Alginates; Experimental study; Nanoencapsulation; Chemical coupling; Polyelectrolyte; Chemical modification; Colon cancer; Nanogel; Internalization; Phototoxicity; Oside polymer; Interpolymer; Chitosan; Manufacturing; Photosensitizer; Tumor cell
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm301858a

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.