PMID- 23327610 OWN - NLM STAT- MEDLINE DCOM- 20130801 LR - 20220410 IS - 1526-4602 (Electronic) IS - 1525-7797 (Print) IS - 1525-7797 (Linking) VI - 14 IP - 2 DP - 2013 Feb 11 TI - Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles. PG - 302-10 LID - 10.1021/bm301858a [doi] 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 mug 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. FAU - Abdelghany, Sharif M AU - Abdelghany SM AD - School of Pharmacy, Centre for Cancer Research and Cell Biology, Queen's University Belfast , 97 Lisburn Road, Belfast, United Kingdom. FAU - Schmid, Daniela AU - Schmid D FAU - Deacon, Jill AU - Deacon J FAU - Jaworski, Jakub AU - Jaworski J FAU - Fay, Francois AU - Fay F FAU - McLaughlin, Kirsty M AU - McLaughlin KM FAU - Gormley, Julie A AU - Gormley JA FAU - Burrows, James F AU - Burrows JF FAU - Longley, Daniel B AU - Longley DB FAU - Donnelly, Ryan F AU - Donnelly RF FAU - Scott, Christopher J AU - Scott CJ LA - eng GR - G1001805/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130131 PL - United States TA - Biomacromolecules JT - Biomacromolecules JID - 100892849 RN - 0 (Alginates) RN - 0 (Antibodies) RN - 0 (Antineoplastic Agents) RN - 0 (Hexuronic Acids) RN - 0 (Photosensitizing Agents) RN - 0 (Porphyrins) RN - 0 (RNA, Small Interfering) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 38673-65-3 (tetra(4-N-methylpyridyl)porphine) RN - 8A5D83Q4RW (Glucuronic Acid) RN - 9012-76-4 (Chitosan) RN - EC 3.4.22.- (Caspase 8) SB - IM MH - Alginates MH - Antibodies/immunology MH - Antineoplastic Agents/*therapeutic use MH - Biological Transport MH - Caspase 8/metabolism MH - Cell Line, Tumor MH - Chitosan/immunology MH - Colorectal Neoplasms/*drug therapy MH - Glucuronic Acid/immunology MH - Hexuronic Acids/immunology MH - Humans MH - Nanoparticles MH - Photochemotherapy MH - Photosensitizing Agents/*therapeutic use MH - Porphyrins/*therapeutic use MH - RNA Interference MH - RNA, Small Interfering MH - Reactive Oxygen Species/metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/immunology PMC - PMC3582313 EDAT- 2013/01/19 06:00 MHDA- 2013/08/02 06:00 CRDT- 2013/01/19 06:00 PHST- 2013/01/19 06:00 [entrez] PHST- 2013/01/19 06:00 [pubmed] PHST- 2013/08/02 06:00 [medline] AID - 10.1021/bm301858a [doi] PST - ppublish SO - Biomacromolecules. 2013 Feb 11;14(2):302-10. doi: 10.1021/bm301858a. Epub 2013 Jan 31.