{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:30:46Z","timestamp":1785403846318,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Polit\u00e9cnico Nacional (IPN) through the Office of Research and Graduate Studies","award":["SIP 2241"],"award-info":[{"award-number":["SIP 2241"]}]},{"award":["SIP 2241"],"award-info":[{"award-number":["SIP 2241"]}],"id":[{"id":"https:\/\/ror.org\/059sp8j34","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SECIHTI","award":["CBF-2026-2186"],"award-info":[{"award-number":["CBF-2026-2186"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteosarcoma, the most common primary malignant bone tumor in adolescents, faces treatment challenges due to metastasis and chemoresistance. This study developed a novel Au@Rh core\u2013shell nanoparticle system functionalized with indocyanine green (ICG) to overcome hypoxia-limited photodynamic therapy (PDT). Au@Rh nanoparticles were synthesized via wet chemistry and characterized by UV-Vis spectroscopy, TEM, and cyclic voltammetry (CV). The system exhibited a core\u2013shell morphology, well-defined crystalline planes, photothermal conversion and electrocatalytic activity. The Au@Rh nanoparticles (109 nm total size, 90 nm Au core, and 15 nm Rh shell) demonstrated dual functionality: the gold core provided photothermal conversion (a 7 \u00b0C temperature increase under NIR irradiation), while the rhodium shell exhibited pH-independent electrocatalytic activity for H2O2 decomposition, generating oxygen to alleviate tumor hypoxia. Crucially, the system showed excellent biocompatibility, with no significant cytotoxicity in both osteosarcoma (HOS) or normal osteoblast (hFOB) cells after 48 h of exposure. When activated by NIR irradiation (808 nm, 16.6 J\/cm2), the complete Au@Rh-ICG system achieved selective 67% cytotoxicity in HOS cells versus only 30% in hFOB cells, demonstrating targeted therapeutic efficacy. These results position Au@Rh-ICG as a promising theranostic platform for osteosarcoma treatment, combining enhanced PDT with photothermal therapy while addressing tumor hypoxia.<\/jats:p>","DOI":"10.3390\/ijms27146253","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:53Z","timestamp":1784023973000},"page":"6253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study of the Cytotoxic Effects of Au@Rh Core\u2013Shell Metal Particles on the Osteosarcoma Cell Line HOS and the hFOB Osteoblast Cell Line"],"prefix":"10.3390","volume":"27","author":[{"given":"Sergio","family":"Zamudio-Lucero","sequence":"first","affiliation":[{"name":"Unidad Profesional Interdisciplinaria de Biotecnolog\u00eda (UPIBI), Instituto Polit\u00e9cnico Nacional (IPN), Av. Acueducto, La Laguna Ticom\u00e1n, Gustavo A. Madero, Ciudad de M\u00e9xico 07340, Mexico"},{"name":"Escuela Superior de Ingenier\u00eda Qu\u00edmica e Industrias Extractivas (ESIQIE), Instituto Polit\u00e9cnico Nacional (IPN), Zacatenco, Edificio 8 1er. Piso, Ciudad de M\u00e9xico 07300, Mexico"},{"name":"Escuela Nacional de Medicina y Homeopat\u00eda (ENMH), Instituto Polit\u00e9cnico Nacional (IPN), Av. Guillermo Massieu Helguera 239, La Escalera, Gustavo A. Madero, Ciudad de M\u00e9xico 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-4632","authenticated-orcid":false,"given":"Mart\u00edn","family":"Trejo-Valdez","sequence":"additional","affiliation":[{"name":"Escuela Superior de Ingenier\u00eda Qu\u00edmica e Industrias Extractivas (ESIQIE), Instituto Polit\u00e9cnico Nacional (IPN), Zacatenco, Edificio 8 1er. 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The management of osteosarcoma in children and adolescents in a resource-limited setting: Quality improvement considerations to improve treatment outcomes. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12786-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1302\/0301-620X.102B6.BJJ-2019-1307.R1","article-title":"Impact of chemotherapy-induced necrosis on event-free and overall survival after preoperative MAP chemotherapy in patients with primary high-grade localized osteosarcoma","volume":"102-B","author":"Tsuda","year":"2020","journal-title":"Bone Jt. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1007\/s11999-016-4851-y","article-title":"A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The Birmingham Classification","volume":"475","author":"Jeys","year":"2017","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1097\/CORR.0000000000000387","article-title":"Neoadjuvant Chemotherapy Followed by Delayed Surgery: Is it Necessary for All Patients With Nonmetastatic High-Grade Pelvic Osteosarcoma?","volume":"476","author":"Xu","year":"2018","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejca.2017.08.013","article-title":"Outcomes in non-metastatic treatment naive extremity osteosarcoma patients treated with a novel non-high dosemethotrexate-based, dose-dense combination chemotherapy regimen \u2018OGS-12\u2019","volume":"85","author":"Bajpai","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.celrep.2014.03.003","article-title":"Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma","volume":"7","author":"Chen","year":"2014","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117212","DOI":"10.1016\/j.bone.2024.117212","article-title":"Global, regional, and national burden and trends analysis of malignant neoplasm of bone and articular cartilage from 1990 to 2021: A systematic analysis for the Global Burden of Disease Study 2021","volume":"188","author":"Lai","year":"2024","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.advop.2025.09.001","article-title":"A relief or new challenges? Global, regional, and national burden of malignant neoplasm of bone and articular cartilage in children and adolescents from 1990 to 2021 and its prediction to 2035","volume":"2","author":"Chen","year":"2025","journal-title":"Adv. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Montgomery, R.M. (2025). Osteosarcoma: Integrating Epidemiological Insights, Genomic Advances, Environmental Determinants, and Novel Therapeutic Strategies in Contemporary Oncological Practice. Preprints, 2025070764.","DOI":"10.20944\/preprints202507.0764.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s43440-023-00504-1","article-title":"The Warburg effect: A score for many instruments in the concert of cancer and cancer niche cells","volume":"75","author":"Jaworska","year":"2023","journal-title":"Pharmacol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1042\/BST20160094","article-title":"The Warburg effect: 80 years on","volume":"44","author":"Potter","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2014.04.001","article-title":"The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism","volume":"356","author":"Lu","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1080\/09553002.2019.1589653","article-title":"The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression","volume":"95","author":"Vaupel","year":"2019","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/jog.13867","article-title":"Warburg effect in Gynecologic cancers","volume":"45","author":"Kobayashi","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Czarnecka, A.M., Synoradzki, K., Firlej, W., Bartnik, E., Sobczuk, P., Fiedorowicz, M., Grieb, P., and Rutkowski, P. (2020). Molecular Biology of Osteosarcoma. Cancers, 12.","DOI":"10.3390\/cancers12082130"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/s41420-024-02236-4","article-title":"Advances in smart nanotechnology-supported photodynamic therapy for cancer","volume":"10","author":"Li","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171582","DOI":"10.1016\/j.cej.2025.171582","article-title":"Nanodynamic therapies for osteosarcoma: Recent advances and future perspectives","volume":"527","author":"Xin","year":"2026","journal-title":"Chem. Eng. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yang, J., Fu, Q., Jiang, H., Li, Y., and Liu, M. (2022). Progress of phototherapy for osteosarcoma and application prospect of blue light photobiomodulation therapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1022973"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Al Jarrah, K., Al-Akhras, M.-A.H., Makhadmeh, G.N., AlZoubi, T., Abuelsamen, A., Zyoud, S.H., Mhareb, M.A., Aziz, A.A., and Abu Noqta, O. (2023). A Novel Approach for Enhanced Osteosarcoma Photodynamic Therapy Using Encapsulated Methylene Blue in Silica Nanoparticles. J. Compos. Sci., 7.","DOI":"10.3390\/jcs7040137"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14453","DOI":"10.1021\/acsami.7b03711","article-title":"Near-Infrared Light Responsive Folate Targeted Gold Nanorods for Combined Photothermal-Chemotherapy of Osteosarcoma","volume":"9","author":"Volsi","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hong, L., Li, J., Luo, Y., Guo, T., Zhang, C., Ou, S., Long, Y., and Hu, Z. (2022). Recent Advances in Strategies for Addressing Hypoxia in Tumor Photodynamic Therapy. Biomolecules, 12.","DOI":"10.3390\/biom12010081"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101587","DOI":"10.1016\/j.mtbio.2025.101587","article-title":"Oxygen tension regulating nanoformulation for the improved photodynamic therapy of hypoxic tumors","volume":"31","author":"Birhan","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/14737159.2022.2157719","article-title":"Association of hypoxia-inducible factor 1 expressions with prognosis role as a survival prognostic biomarker in the patients with osteosarcoma: A meta-analysis","volume":"22","author":"Khojastehnezhad","year":"2022","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13018-019-1101-5","article-title":"Clinicopathological and prognostic value of hypoxia-inducible factor-1\u03b1 in patients with bone tumor: A systematic review and meta-analysis","volume":"14","author":"Luo","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cell.2016.07.032","article-title":"Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche","volume":"166","author":"Clever","year":"2016","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.1038\/s41598-017-14401-0","article-title":"Near-infrared photothermal\/photodynamic therapy with indocyanine green induces apoptosis of hepatocellular carcinoma cells through oxidative stress","volume":"7","author":"Shirata","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jconrel.2017.05.015","article-title":"Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres","volume":"258","author":"Li","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2001862","DOI":"10.1002\/adma.202001862","article-title":"A Porous Au@Rh Bimetallic Core-Shell Nanostructure as an H2O2-Driven Oxygenerator to Alleviate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy","volume":"32","author":"Wang","year":"2020","journal-title":"Adv. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Winkler, R., Ciria, M., Ahmad, M., Plank, H., and Marcuello, C. (2023). A Review of the Current State of Magnetic Force Microscopy to Unravel the Magnetic Properties of Nanomaterials Applied in Biological Systems and Future Directions for Quantum Technologies. Nanomaterials, 13.","DOI":"10.3390\/nano13182585"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s11671-026-04566-x","article-title":"Nanoparticle-based mechanistic and multifunctional strategies for targeted osteosarcoma therapy","volume":"21","author":"Cai","year":"2026","journal-title":"Nanoscale Res. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e407","DOI":"10.1038\/am.2017.114","article-title":"Bimetallic AuRh nanodendrites consisting of Au icosahedron cores and atomically ultrathin Rh nanoplate shells: Synthesis and light-enhanced catalytic activity","volume":"9","author":"Kang","year":"2017","journal-title":"NPG Asia Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7685","DOI":"10.1002\/chem.202001112","article-title":"Rhodium Nanoparticles as a Novel Photosensitizing Agent in Photodynamic Therapy against Cancer","volume":"26","author":"Machuca","year":"2020","journal-title":"Chemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1021\/acsnano.8b02698","article-title":"Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy","volume":"12","author":"Kang","year":"2018","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.colsurfb.2012.11.017","article-title":"Au(III)\u2013CTAB reduction by ascorbic acid: Preparation and characterization of gold nanoparticles","volume":"104","author":"Khan","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2205511","DOI":"10.1002\/smll.202205511","article-title":"RhRu Alloy-Anchored MXene Nanozyme for Synergistic Osteosarcoma Therapy","volume":"19","author":"Liang","year":"2023","journal-title":"Small"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1039\/c8pp00271a","article-title":"Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer","volume":"17","author":"Bruce","year":"2018","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41392-023-01536-y","article-title":"Nanomedicine in cancer therapy","volume":"8","author":"Fan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41568-025-00847-2","article-title":"Advancing engineering design strategies for targeted cancer nanomedicine","volume":"25","author":"Gomerdinger","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Compton, R.G., and Banks, C.E. (2018). Understanding Voltammetry, World Scientific. [3rd ed.].","DOI":"10.1142\/q0155"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s10856-019-6221-2","article-title":"Impact of gold nanoparticles shape on their cytotoxicity against human osteoblast and osteosarcoma in in vitro model. Evaluation of the safety of use and anti-cancer potential","volume":"30","author":"Steckiewicz","year":"2019","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s10856-017-5902-y","article-title":"Size and shape-dependent cytotoxicity profile of gold nanoparticles for biomedical applications","volume":"28","author":"Malankowska","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Solarte, D.L.G., Rau, S.J., Hellwig, E., Vach, K., and Al-Ahmad, A. (2022). Antimicrobial Behavior and Cytotoxicity of Indocyanine Green in Combination with Visible Light and Water-Filtered Infrared A Radiation against Periodontal Bacteria and Subgingival Biofilm. Biomedicines, 10.","DOI":"10.3390\/biomedicines10050956"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"932","DOI":"10.3897\/folmed.64.e67475","article-title":"Evaluation of Indocyanine-Mediated Photodynamic Therapy Cytotoxicity in Human Osteoblast-Like Cells: An In Vitro Study","volume":"64","author":"Aghayan","year":"2022","journal-title":"Folia Medica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12951-021-01201-y","article-title":"Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms","volume":"20","author":"Wang","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pdpdt.2017.08.010","article-title":"Impact of genotypic and phenotypic differences in sarcoma models on the outcome of photochemical internalization (PCI) of bleomycin","volume":"20","author":"Olsen","year":"2017","journal-title":"Photodiagnosis Photodyn. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:14:36Z","timestamp":1784024076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":46,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146253"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146253","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}