{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:44:27Z","timestamp":1759365867750,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UID\/00645\/2023","UIDB\/04138\/2020","UIDP\/04138\/2020"],"award-info":[{"award-number":["UID\/00645\/2023","UIDB\/04138\/2020","UIDP\/04138\/2020"]}]},{"name":"PhD fellowships","award":["SFRH\/BD\/05377\/2021","UI\/BD\/153626\/2022"],"award-info":[{"award-number":["SFRH\/BD\/05377\/2021","UI\/BD\/153626\/2022"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Head and neck cancer (HNC) is the sixth most common cancer worldwide, with a high mortality, particularly from head and neck squamous cell carcinoma (HNSCC). Although some therapeutic strategies are available, they might cause severe side effects. For example, surgery may result in disfigurement and functional loss, severely impacting the patient\u2019s quality of life. Thus, minimally invasive and more effective alternatives are needed. Gold nanoparticle (AuNP)-mediated photothermal therapy (PTT) is a promising approach for HNC, which relies on AuNP photothermal efficiency and tumor localization. This study aimed to synthesize and characterize AuNPs, evaluate their safety without laser activation, and assess their efficacy with laser activation. Methods and Results: Their physicochemical and photostability over three months and sterility were confirmed. In vitro safety was tested using human non-cancerous and HNC cell lines, while in vivo biocompatibility was evaluated in the hen\u2019s egg chorioallantoic membrane (CAM) model, with no adverse effects observed. Upon laser activation, AuNPs reduced HNC cell viability by 50\u201370%, including HNSCC lines. In vivo biodistribution studies showed that AuNPs remained at the injection site for up to one month without toxicity. Conclusions: Overall, the developed AuNP formulation demonstrates stability, biocompatibility, and prolonged local retention, key attributes for effective and targeted PTT. These findings support the potential of AuNP-mediated photothermal therapy as a promising treatment modality for HNC, although further preclinical and clinical studies are needed to optimize treatment parameters.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101283","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:06:02Z","timestamp":1759316762000},"page":"1283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Towards a Less Invasive Treatment for Head and Neck Cancer: Initial Evaluation of Gold Nanoparticle-Mediated Photothermal Therapy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-2157","authenticated-orcid":false,"given":"Mariana Neves","family":"Amaral","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-4580","authenticated-orcid":false,"given":"\u00cdris","family":"Neto","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Mitza","family":"Cabral","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-6588","authenticated-orcid":false,"given":"Daniela","family":"Nunes","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4202-7047","authenticated-orcid":false,"given":"Elvira","family":"Fortunato","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-7669","authenticated-orcid":false,"given":"Rodrigo","family":"Martins","sequence":"additional","affiliation":[{"name":"CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon and CEMOP\/UNINOVA, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-0910","authenticated-orcid":false,"given":"Carla","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"REQUIMTE\/CQFB, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Ant\u00f3nio P.","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Av. Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-8746","authenticated-orcid":false,"given":"Jos\u00e9","family":"Catarino","sequence":"additional","affiliation":[{"name":"CECAV, Centro de Ci\u00eancia Animal e Veterin\u00e1ria-Faculdade de Medicina Veterin\u00e1ria, Universidade Lus\u00f3fona, Centro Universit\u00e1rio de Lisboa, Campo Grande 376, 1749-024 Lisbon, Portugal"},{"name":"I-MVET (Investiga\u00e7\u00e3o em Medicina Veterin\u00e1ria), Faculdade de Medicina Veterin\u00e1ria, Universidade Lus\u00f3fona, 1749-024 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-3602","authenticated-orcid":false,"given":"Pedro","family":"Fa\u00edsca","sequence":"additional","affiliation":[{"name":"CECAV, Centro de Ci\u00eancia Animal e Veterin\u00e1ria-Faculdade de Medicina Veterin\u00e1ria, Universidade Lus\u00f3fona, Centro Universit\u00e1rio de Lisboa, Campo Grande 376, 1749-024 Lisbon, Portugal"},{"name":"I-MVET (Investiga\u00e7\u00e3o em Medicina Veterin\u00e1ria), Faculdade de Medicina Veterin\u00e1ria, Universidade Lus\u00f3fona, 1749-024 Lisbon, Portugal"}]},{"given":"Hugo Alexandre","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4339-0550","authenticated-orcid":false,"given":"Jo\u00e3o M. P.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-7226","authenticated-orcid":false,"given":"Maria Manuela","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-4031","authenticated-orcid":false,"given":"Catarina Pinto","family":"Reis","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","first-page":"430","article-title":"Advances in Nanomaterials for the Diagnosis and Treatment of Head and Neck Cancers: A Review","volume":"25","author":"Yu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57367","DOI":"10.18632\/oncotarget.10350","article-title":"Local Hyperthermia in Head and Neck Cancer: Mechanism, Application and Advance","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101118","DOI":"10.1016\/j.neo.2024.101118","article-title":"Recent Advances of Photodiagnosis and Treatment for Head and Neck Squamous Cell Carcinoma","volume":"60","author":"Zhang","year":"2025","journal-title":"Neoplasia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e702","DOI":"10.1002\/mco2.702","article-title":"Head and Neck Cancer: Pathogenesis and Targeted Therapy","volume":"5","author":"Liu","year":"2024","journal-title":"MedComm"},{"key":"ref_5","first-page":"e132","article-title":"Factors Associated with the Quality of Life of Subjects with Facial Disfigurement Due to Surgical Treatment of Head and Neck Cancer","volume":"23","author":"Nogueira","year":"2018","journal-title":"Med. Oral Patol. Oral Cirug\u00eda Bucal"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41392-022-01297-0","article-title":"Targeted Therapy for Head and Neck Cancer: Signaling Pathways and Clinical Studies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, A.M., Weaver, A.N., Acosta, P., Harris, L., and Bowles, D.W. (2024). Review of Current and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16203488"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, Y., Han, J., Zhu, Y., Huang, N., and Qu, N. (2025). New Advances in the Therapeutic Strategy of Head and Neck Squamous Cell Carcinoma: A Review of Latest Therapies and Cutting-Edge Research. Biochim. Biophys. Acta-Rev. Cancer, 1880.","DOI":"10.1016\/j.bbcan.2024.189230"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100518","DOI":"10.1016\/j.oor.2024.100518","article-title":"The Impact of Facial Disfigurement and Self-Image Anxiety on the Quality of Life of Head and Neck Cancer Patients","volume":"10","author":"Bhandari","year":"2024","journal-title":"Oral Oncol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1002\/lary.32064","article-title":"The Evolution of Multidisciplinary Head and Neck Cancer Treatment","volume":"135","author":"Contrera","year":"2025","journal-title":"Laryngoscope"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Amaral, M.N., Fa\u00edsca, P., Ferreira, H.A., Gaspar, M.M., and Reis, C.P. (2022). Current Insights and Progress in the Clinical Management of Head and Neck Cancer. Cancers, 14.","DOI":"10.3390\/cancers14246079"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vines, J.B., Yoon, J.-H., Ryu, N.-E., Lim, D.-J., and Park, H. (2019). Gold Nanoparticles for Photothermal Cancer Therapy. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00167"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kim, D., Paik, J., and Kim, H. (2023). Effect of Gold Nanoparticles Distribution Radius on Photothermal Therapy Efficacy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-39040-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9327","DOI":"10.2147\/IJN.S525462","article-title":"Effect of Photothermal Therapy Using Gold Nanoparticles Conjugated with Hyaluronic Acid in an Intracranial Murine Glioblastoma Model","volume":"20","author":"Foti","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1021\/nl201400z","article-title":"Copper Selenide Nanocrystals for Photothermal Therapy","volume":"11","author":"Hessel","year":"2011","journal-title":"Nano Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zhou, F., Wang, C., Hu, L., and Guo, P. (2022). Nanostructures as Photothermal Agents in Tumor Treatment. Molecules, 28.","DOI":"10.3390\/molecules28010277"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Qi, K., Sun, B., Liu, S., and Zhang, M. (2023). Research Progress on Carbon Materials in Tumor Photothermal Therapy. Biomed. Pharmacother., 165.","DOI":"10.1016\/j.biopha.2023.115070"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xie, B., Xiao, Z., Ling, J., Peng, Y., and Chen, T. (2025). Exploring the Application of Metal-Based Photothermal Agents in Photothermal Therapy Combined with Immune Checkpoint Therapy. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1553158"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119388","DOI":"10.1016\/j.jlumin.2022.119388","article-title":"Significant Effect on the Photo Conversion Performance of Non-Stoichiometric Tungsten Oxide with Various Reaction Solvents","volume":"252","author":"Li","year":"2022","journal-title":"J. Lumin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1038\/s41467-020-16513-0","article-title":"Marriage of Black Phosphorus and Cu2+ as Effective Photothermal Agents for PET-Guided Combination Cancer Therapy","volume":"11","author":"Hu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, R., Huang, Z., Xiao, Y., Huang, T., and Ming, J. (2023). Photothermal Therapy of Copper Incorporated Nanomaterials for Biomedicine. Biomater. Res., 27.","DOI":"10.1186\/s40824-023-00461-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2500652","DOI":"10.1002\/advs.202500652","article-title":"A Copper-Based Photothermal-Responsive Nanoplatform Reprograms Tumor Immunogenicity via Self-Amplified Cuproptosis for Synergistic Cancer Therapy","volume":"12","author":"Cheng","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Salimi, M., Mosca, S., Gardner, B., Palombo, F., Matousek, P., and Stone, N. (2022). Nanoparticle-Mediated Photothermal Therapy Limitation in Clinical Applications Regarding Pain Management. Nanomaterials, 12.","DOI":"10.3390\/nano12060922"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14443","DOI":"10.1039\/D3RA02620E","article-title":"Nanomaterials for Photothermal Cancer Therapy","volume":"13","author":"Duan","year":"2023","journal-title":"RSC Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00204-014-1376-6","article-title":"Toxicity of Single-Walled Carbon Nanotubes","volume":"90","author":"Ong","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27638","DOI":"10.1021\/acsami.3c03611","article-title":"Biogenic Copper Selenide Nanoparticles for Near-Infrared Photothermal Therapy Application","volume":"15","author":"Wang","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lagos, K.J., Buzz\u00e1, H.H., Bagnato, V.S., and Romero, M.P. (2021). Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202111.0119.v1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1515\/ejnm-2013-0006","article-title":"Tumor Photothermolysis: Using Carbon Nanomaterials for Cancer Therapy","volume":"5","author":"Sawdon","year":"2013","journal-title":"Eur. J. Nanomed."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cao, J., Qi, J., Lin, X., Xiong, Y., He, F., Deng, W., and Liu, G. (2021). Biomimetic Black Phosphorus Nanosheet-Based Drug Delivery System for Targeted Photothermal-Chemo Cancer Therapy. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.707208"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Riley, R.S., and Day, E.S. (2017). Gold Nanoparticle-mediated Photothermal Therapy: Applications and Opportunities for Multimodal Cancer Treatment. WIREs Nanomed. Nanobiotechnol., 9.","DOI":"10.1002\/wnan.1449"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106215","DOI":"10.1016\/j.jddst.2024.106215","article-title":"Gold Nanoparticles for Photothermal Therapy\u2014Influence of Experimental Conditions on the Properties of Resulting AuNPs","volume":"101","author":"Amaral","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Taylor, M.L., Wilson, R.E., Amrhein, K.D., and Huang, X. (2022). Gold Nanorod-Assisted Photothermal Therapy and Improvement Strategies. Bioengineering, 9.","DOI":"10.3390\/bioengineering9050200"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ferreira-Gon\u00e7alves, T., Gaspar, M.M., Coelho, J.M.P., Marques, V., Viana, A.S., Ascens\u00e3o, L., Carvalho, L., Rodrigues, C.M.P., Ferreira, H.A., and Ferreira, D. (2022). The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment. Biomolecules, 12.","DOI":"10.3390\/biom12010071"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lopes, J., Ferreira-Gon\u00e7alves, T., Ascens\u00e3o, L., Viana, A.S., Carvalho, L., Catarino, J., Fa\u00edsca, P., Oliva, A., de Barros, D.P.C., and Rodrigues, C.M.P. (2023). Safety of Gold Nanoparticles: From In Vitro to In Vivo Testing Array Checklist. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041120"},{"key":"ref_35","first-page":"123659","article-title":"Rational Approach to Design Gold Nanoparticles for Photothermal Therapy: The Effect of Gold Salt on Physico-Chemical, Optical and Biological Properties","volume":"650","author":"Nunes","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Amaral, M., Charmier, A.J., Afonso, R.A., Catarino, J., Fa\u00edsca, P., Carvalho, L., Ascens\u00e3o, L., Coelho, J.M.P., Gaspar, M.M., and Reis, C.P. (2021). Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward. Cancers, 13.","DOI":"10.3390\/cancers13061242"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pinho, S., Ferreira-Gon\u00e7alves, T., Lopes, J., Amaral, M.N., Viana, A.S., Coelho, J.M.P., Gaspar, M.M., and Reis, C.P. (2024). A Step Forward for the Treatment of Localized Prostate Cancer Using Gold Nanoparticles Combined with Laser Irradiation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084488"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"124952","DOI":"10.1016\/j.ijpharm.2024.124952","article-title":"Combination of Gold Nanoparticles with Near-Infrared Light as an Alternative Approach for Melanoma Management","volume":"668","author":"Lopes","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Amaral, M.N., Kumar, P., Fa\u00edsca, P., Ferreira, H.A., Coelho, J.M.P., Gaspar, M.M., and Reis, C.P. (2025). Gold Nanoparticle-Mediated Photothermal Therapy: Expanding the Frontiers of Cancer Treatment and Theragnostics. Biomed. Pharmacother., 190.","DOI":"10.1016\/j.biopha.2025.118399"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s12020-019-02009-5","article-title":"Establishment and Characterization of a New Patient-Derived Anaplastic Thyroid Cancer Cell Line (C3948), Obtained through Fine-Needle Aspiration Cytology","volume":"66","author":"Pinto","year":"2019","journal-title":"Endocrine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7695","DOI":"10.4049\/jimmunol.176.12.7695","article-title":"Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative P53 Makes Their Growth Independent of HER-2\/Neu Expression","volume":"176","author":"Pannellini","year":"2006","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Amaral, M., Martins, A.S., Catarino, J., Fa\u00edsca, P., Kumar, P., Pinto, J.F., Pinto, R., Correia, I., Ascens\u00e3o, L., and Afonso, R.A. (2020). How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight Using Ex-Vivo, In Silico, and In Vivo Models. Biomolecules, 10.","DOI":"10.3390\/biom10050675"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34444","DOI":"10.1021\/acsami.5c08389","article-title":"3D-Printed Cellulose Aerogels Minimally Cross-Linked with Polyurea: A Robust Strategy for Tissue Engineering","volume":"17","author":"Raptopoulos","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1055\/s-0041-1736474","article-title":"Size-Adjustable Nano-Drug Delivery Systems for Enhanced Tumor Retention and Penetration","volume":"03","author":"Deng","year":"2021","journal-title":"Pharm. Front."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.apsb.2024.11.012","article-title":"Size-Transformable Nanotherapeutics for Cancer Therapy","volume":"15","author":"Ma","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1007\/s00216-023-04540-x","article-title":"Quantification of Monodisperse and Biocompatible Gold Nanoparticles by Single-Particle ICP-MS","volume":"415","author":"Frickenstein","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3390\/analytica4020020","article-title":"Gold Nanoparticles: A Didactic Step-by-Step of the Synthesis Using the Turkevich Method, Mechanisms, and Characterizations","volume":"4","author":"Oliveira","year":"2023","journal-title":"Analytica"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"124799","DOI":"10.1016\/j.ijpharm.2024.124799","article-title":"Effects of Nanoparticle Size, Shape, and Zeta Potential on Drug Delivery","volume":"666","author":"Kaplan","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pourali, P., Benada, O., P\u00e1tek, M., Neuh\u00f6ferov\u00e1, E., Dzmitruk, V., and Benson, V. (2021). Response of Biological Gold Nanoparticles to Different PH Values: Is It Possible to Prepare Both Negatively and Positively Charged Nanoparticles?. Appl. Sci., 11.","DOI":"10.3390\/app112311559"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/02726351.2022.2078253","article-title":"Easy Synthesis of 4-Quinonimine Functionalized Gold Nanoparticles in Stable Aqueous Colloidal State","volume":"41","author":"Kundu","year":"2023","journal-title":"Part. Sci. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jconrel.2016.06.017","article-title":"DLS and Zeta Potential\u2014What They Are and What They Are Not?","volume":"235","author":"Bhattacharjee","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13082","DOI":"10.1021\/acs.jpcc.8b00388","article-title":"Gold Nanostars in Plasmonic Photothermal Therapy: The Role of Tip Heads in the Thermoplasmonic Landscape","volume":"122","author":"Chatterjee","year":"2018","journal-title":"J. Phys. Chem. C"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14932","DOI":"10.1039\/C6NR04045D","article-title":"One-Step Fabrication of Hollow-Channel Gold Nanoflowers with Excellent Catalytic Performance and Large Single-Particle SERS Activity","volume":"8","author":"Ye","year":"2016","journal-title":"Nanoscale"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kumar, P.P.P., and Lim, D.-K. (2023). Photothermal Effect of Gold Nanoparticles as a Nanomedicine for Diagnosis and Therapeutics. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092349"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bernal-Ch\u00e1vez, S.A., Del Prado-Audelo, M.L., Caballero-Flor\u00e1n, I.H., Giraldo-Gomez, D.M., Figueroa-Gonzalez, G., Reyes-Hernandez, O.D., Gonz\u00e1lez-Del Carmen, M., Gonz\u00e1lez-Torres, M., Cort\u00e9s, H., and Leyva-G\u00f3mez, G. (2021). Insights into Terminal Sterilization Processes of Nanoparticles for Biomedical Applications. Molecules, 26.","DOI":"10.3390\/molecules26072068"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111087","DOI":"10.1016\/j.msec.2020.111087","article-title":"A New Way to Prepare Gold Nanoparticles by Sputtering\u2014Sterilization, Stability and Other Properties","volume":"115","author":"Ulbrich","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/smll.200901006","article-title":"Sterilization Matters: Consequences of Different Sterilization Techniques on Gold Nanoparticles","volume":"6","author":"Pelaz","year":"2010","journal-title":"Small"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Buhr, C.R., Wiesmann, N., Tanner, R.C., Brieger, J., and Eckrich, J. (2020). The Chorioallantoic Membrane Assay in Nanotoxicological Research\u2014An Alternative for In Vivo Experimentation. Nanomaterials, 10.","DOI":"10.3390\/nano10122328"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1177\/1091581816672187","article-title":"The Hen\u2019s Egg Test on Chorioallantoic Membrane","volume":"35","author":"Tur","year":"2016","journal-title":"Int. J. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19626","DOI":"10.1021\/acsnano.2c03990","article-title":"Bridging the In Vitro to In Vivo Gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for In Vivo Studies","volume":"16","author":"Butler","year":"2022","journal-title":"ACS Nano"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s11671-023-03882-w","article-title":"Effect of Nanoparticle Size on Their Distribution and Retention in Chronic Inflammation Sites","volume":"18","author":"Aldayel","year":"2023","journal-title":"Discov. Nano"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4155\/tde.12.21","article-title":"Size Matters: Gold Nanoparticles in Targeted Cancer Drug Delivery","volume":"3","author":"Dreaden","year":"2012","journal-title":"Ther. Deliv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.biomaterials.2007.12.037","article-title":"Particle Size-Dependent Organ Distribution of Gold Nanoparticles after Intravenous Administration","volume":"29","author":"Hagens","year":"2008","journal-title":"Biomaterials"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cooley, M.B., Wegierak, D., and Exner, A.A. (2024). Using Imaging Modalities to Predict Nanoparticle Distribution and Treatment Efficacy in Solid Tumors: The Growing Role of Ultrasound. WIREs Nanomed. Nanobiotechnol., 16.","DOI":"10.1002\/wnan.1957"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:14:26Z","timestamp":1759317266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pharmaceutics17101283"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17101283","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}