{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:08:30Z","timestamp":1793660910034,"version":"4.5.1"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation","doi-asserted-by":"publisher","award":["98337"],"award-info":[{"award-number":["98337"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Johannesburg","award":["98337"],"award-info":[{"award-number":["98337"]}]},{"name":"National Laser Centre","award":["98337"],"award-info":[{"award-number":["98337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper\u2013gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment.<\/jats:p>","DOI":"10.3390\/ijms24031902","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:51:37Z","timestamp":1674096697000},"page":"1902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Photodynamic Therapy of Aluminum Phthalocyanine Tetra Sodium 2-Mercaptoacetate Linked to PEGylated Copper\u2013Gold Bimetallic Nanoparticles on Colon Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3368-7147","authenticated-orcid":false,"given":"Nokuphila Winifred Nompumelelo","family":"Simelane","sequence":"first","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2373-2365","authenticated-orcid":false,"given":"Gauta Gold","family":"Matlou","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-827X","authenticated-orcid":false,"given":"Heidi","family":"Abrahamse","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"928010","DOI":"10.3389\/fnano.2022.928010","article-title":"Zinc Phthalocyanine Tetrasulfonate-Loaded Ag@mSiO2 Nanoparticles for Active Targeted Photodynamic Therapy of Colorectal Cancer","volume":"4","author":"Montaseri","year":"2022","journal-title":"Front. Nanotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3892\/ol.2016.4179","article-title":"Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer","volume":"11","author":"Sun","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"156","DOI":"10.18632\/oncotarget.28171","article-title":"Synthesis of a novel nanobioconjugate for targeted photodynamic therapy of colon cancer enhanced with cannabidiol","volume":"13","author":"Nkune","year":"2022","journal-title":"Oncotarget"},{"key":"ref_5","first-page":"2010","article-title":"Photochemical and photophysical properties of metallophthalocyanines","volume":"Volume 7","author":"Kadish","year":"2010","journal-title":"The handbook of Pophyrin Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1039\/c1pp05014a","article-title":"Targeted photodynamic therapy of breast cancer cells using antibody-phthalocyanine-gold nanoparticle conjugates","volume":"10","author":"Stuchinskaya","year":"2011","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/nm.2554","article-title":"Cancer cell-selective in vivo Near Infrared Photoimmunotherapy targeting specific membrane molecules","volume":"17","author":"Mitsunaga","year":"2011","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00775-005-0652-6","article-title":"Effects of heavy central metal on the ground and excited states of chlorophyll","volume":"10","author":"Skania","year":"2005","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jlumin.2018.09.054","article-title":"Evaluation of the photosensitizing properties of zinc and indium tetra cinnamic acid phthalocyanines linked to magnetic nanoparticles on human breast adenocarcinoma cells","volume":"205","author":"Matlou","year":"2019","journal-title":"J. Lumin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jphotochem.2019.01.025","article-title":"Physicochemical and photodynamic antimicrobial chemotherapy activity of morpholine-substituted phthalocyanines: Effect of point of substitution and central metal","volume":"374","author":"Sindelo","year":"2019","journal-title":"J. Photochem. Photobiol. A Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1016\/j.tet.2012.01.004","article-title":"Synthesis of unsymmetrical phthalocyanines: A brief overview","volume":"68","author":"Wang","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jphotochem.2008.09.011","article-title":"Comparison between non-peripherally and peripherally tetra-substituted zinc (II) phthalocyanines as photosensitizers: Synthesis, spectroscopic, photochemical and photobiological properties","volume":"201","author":"Ke","year":"2009","journal-title":"J. Photochem. Photobiol. A Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.dyepig.2015.12.017","article-title":"Phthalocyanines with bulky substituents at non-peripheral positions\u2014Synthesis and physico-chemical properties","volume":"127","author":"Tillo","year":"2016","journal-title":"Dye. Pigment."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100136","DOI":"10.1016\/j.jpap.2022.100136","article-title":"Active targeted photodynamic therapeutic effect of silver-based nanohybrids on melanoma cancer cells","volume":"11","author":"Montaseri","year":"2022","journal-title":"J. Photochem. Photobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.18632\/oncotarget.27029","article-title":"Photodynamic therapy of cervical cancer by eradication of cervical cancer cells and cervical cancer stem cells","volume":"10","author":"Chizenga","year":"2019","journal-title":"Oncotarget"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jphotobiol.2016.05.008","article-title":"Photodynamic evaluation of tetracarboxy-phthalocyanines in model systems","volume":"161","author":"Alonso","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1010428317734691","DOI":"10.1177\/1010428317734691","article-title":"Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells","volume":"39","author":"Hodgkinson","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1533033818791795","DOI":"10.1177\/1533033818791795","article-title":"Photodynamic therapy for metastatic melanoma treatment: A review","volume":"17","author":"Honors","year":"2018","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Crous, A., and Abrahamse, H. (2020). Effective gold nanoparticle-antibody-mediated drug delivery for photodynamic therapy of lung cancer stem cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113742"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, G., Zhang, W., Luo, N., Xue, Z., Hu, Q., Zeng, W., and Xu, J. (2021). Bimetallic nanocrystals: Structure, controllable synthesis and applications in catalysis, energy and sensing. Nanomaterials, 11.","DOI":"10.3390\/nano11081926"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kruger, C.A., and Abrahamse, H. (2018). Utilisation of targeted nanoparticle photosensitiser drug delivery systems for the enhancement of photodynamic therapy. Molecules, 23.","DOI":"10.3390\/molecules23102628"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.impact.2020.100253","article-title":"Smart nanocarriers for cancer treatment: Clinical impact and safety","volume":"20","author":"Liao","year":"2020","journal-title":"NanoImpact"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7984","DOI":"10.1039\/D1BM01398J","article-title":"Passive targeting of high-grade gliomas: Via the EPR effect: A closed path for metallic nanoparticles?","volume":"9","author":"Caro","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jconrel.2014.03.057","article-title":"EPR: Evidence and fallacy","volume":"190","author":"Nichols","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jconrel.2014.06.046","article-title":"PEG\u2014A versatile conjugating ligand for drugs and drug delivery systems","volume":"192","author":"Kolate","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.1039\/C7NR01110E","article-title":"Highly water-stable rare ternary Ag-Au-Se nanocomposites as long blood circulation time X-ray computed tomography contrast agents","volume":"9","author":"Caro","year":"2017","journal-title":"Nanoscale"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12309","DOI":"10.1039\/C7NJ01716B","article-title":"Synthesis and photophysical studies of asymmetric zinc phthalocyanine\u2013magnetic nanoparticle conjugates","volume":"41","author":"Matlou","year":"2017","journal-title":"New J. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0143-7208(92)80009-C","article-title":"Efficient synthesis of phthalocyanines and related macrocyclic compounds in the presence of organic bases","volume":"18","author":"Schnurpfeil","year":"1992","journal-title":"Dye. Pigment."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3998\/ark.5550190.0011.104","article-title":"Synthesis of substituted phthalocyanines","volume":"2010","author":"Nemykina","year":"2010","journal-title":"Arkivoc"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7047","DOI":"10.1039\/c2dt30244f","article-title":"Highly selective thioalcohol modified phthalocyanine sensors for Ag(i) and Pd(ii) based on target induced J- and H-type aggregations: Synthesis, electrochemistry and peripheral metal ion binding studies","volume":"41","author":"Kandaz","year":"2012","journal-title":"Dalton Trans."},{"key":"ref_31","unstructured":"Leznoff, C.C., and Lever, B. (1989). Phthalocyanines-Properties and Applications, VCH Publications."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.saa.2019.02.005","article-title":"Effect of symmetry and metal nanoparticles on the photophysicochemical and photodynamic therapy properties of cinnamic acid zinc phthalocyanine","volume":"214","author":"Matlou","year":"2019","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jphotochem.2018.04.011","article-title":"In-situ synthesis of gold nanoparticles on graphene quantum dots-phthalocyanine nanoplatforms: First description of the photophysical and surface enhanced Raman scattering behaviour","volume":"359","author":"Nwahara","year":"2018","journal-title":"J. Photochem. Photobiol. A Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1021\/ma00138a033","article-title":"Syntheses and characterization of heteroatom-bridged metal-free phthalocyanine network polymers and model compounds","volume":"17","author":"Snow","year":"1984","journal-title":"Macromolecules"},{"key":"ref_35","unstructured":"Jenkins, R., and Synder, R. (1998). Introduction to X-ray Diffractometry, Wiley and Sons."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11051-008-9435-7","article-title":"A comparison of atomic force microscopy (AFM) and dynamic light scattering (DLS) methods to characterize nanoparticle size distributions","volume":"10","author":"Hoo","year":"2008","journal-title":"J. Nanopart. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1021\/ja00083a015","article-title":"Photochemical formation of the anion radical of zinc phthalocyanine and analysis of the absorption and magnetic circular dichroism spectral data. Assignment of the opticla spectrum of [ZnPc(-3)]-","volume":"116","author":"Mack","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0009-2614(95)01335-0","article-title":"Geometry and electronic structure of porphyrins and porphyrazines","volume":"248","author":"Lamoen","year":"1996","journal-title":"Chem. Phys. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1016\/j.poly.2007.01.018","article-title":"Synthesis and solvent effects on the electronic absorption and fluorescence spectral properties of substituted zinc phthalocyanines","volume":"26","author":"Nyokong","year":"2007","journal-title":"Polyhedron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1470-2045(04)01529-3","article-title":"The present and future role of photodynamic therapy in cancer treatment","volume":"5","author":"Brown","year":"2004","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.apsb.2017.09.003","article-title":"An updated overview on the development of new photosensitizers for anticancer photodynamic therapy","volume":"8","author":"Zhang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_43","first-page":"83","article-title":"Photodynamic therapy in cancer treatment\u2014An update review","volume":"5","author":"Terra","year":"2019","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chakraborti, S. (2022). Handbook of Oxidative Stress in Cancer: Therapeutic Aspects, Springler Nature.","DOI":"10.1007\/978-981-16-5422-0"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Matlou, G.G., and Abrahamse, H. (2021). Hybrid inorganic-organic core-shell nanodrug systems in targeted photodynamic therapy of cancer. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111773"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s42452-020-2279-1","article-title":"Biogenic copper nanoparticles and their applications: A review","volume":"2","year":"2020","journal-title":"SN Appl. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"691697","DOI":"10.3389\/fchem.2021.691697","article-title":"Photodynamic Therapy\u2014Current Limitations and Novel Approaches","volume":"9","author":"Gunaydin","year":"2021","journal-title":"Front. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mokoena, D.R., Blassan, G.P., and Abrahamse, H. (2021). Photodynamic Therapy Induced Cell Death Mechanisms in Breast Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910506"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20150942","article-title":"New photosensitizers for photodynamic therapy","volume":"473","author":"Abrahamse","year":"2016","journal-title":"Biochemistry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"383027","DOI":"10.1155\/2014\/383027","article-title":"Multiorganelle localization of metallated phthalocyanine photosensitizer in colorectal cancer cells (DLD-1 and CaCo-2) enhances efficacy of photodynamic therapy","volume":"2014","author":"Sekhejane","year":"2014","journal-title":"Int. J. Photoenergy"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10228","DOI":"10.3390\/ijms160510228","article-title":"Cell death pathways and phthalocyanine as an efficient agent for photodynamic cancer therapy","volume":"16","author":"Abrahamse","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Nkune, N.W., Matlou, G.G., and Abrahamse, H. (2022). Photodynamic Therapy Efficacy of Novel Zinc Phthalocyanine Tetra Sodium 2-Mercaptoacetate Combined with Cannabidiol on Metastatic Melanoma. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112418"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jcis.2004.01.071","article-title":"Synthesis of high-concentration Cu nanoparticles in aqueous CTAB solutions","volume":"273","author":"Wu","year":"2004","journal-title":"J. Colloid Interface Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1080\/01932691.2010.497682","article-title":"Synthesis and Characterization of Bimetallic Copper-Gold Nanoparticles","volume":"33","author":"Larios","year":"2012","journal-title":"J. Dispers. Sci. Technol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:15Z","timestamp":1760119755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24031902"],"URL":"https:\/\/doi.org\/10.3390\/ijms24031902","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}