{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:13:31Z","timestamp":1789787611457,"version":"4.0.1"},"reference-count":90,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Scholarships Foundation (IKY)","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 (177Lu) resulted in an additional therapeutic effect. Functionalization was accomplished at high percentages and radiolabeling was robust. The high cytotoxic effect of our radiolabeled and non-radiolabeled nanostructures was proven in vitro against five different breast cancer cell lines. The ex vivo biodistribution in tumor-bearing mice was investigated with three different ways of administration. The intratumoral administration of our functionalized radionanoconjugates showed high tumor accumulation and retention at the tumor site. Finally, our therapeutic efficacy study performed over a 50-day period against an aggressive triple-negative breast cancer cell line (4T1) demonstrated enhanced tumor growth retention, thus identifying the developed nanoparticles as a promising nanobrachytherapy agent against breast cancer.<\/jats:p>","DOI":"10.3390\/molecules29051030","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:52:55Z","timestamp":1709034775000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["177Lu-Labeled Iron Oxide Nanoparticles Functionalized with Doxorubicin and Bevacizumab as Nanobrachytherapy Agents against Breast Cancer"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2091-0234","authenticated-orcid":false,"given":"Evangelia-Alexandra","family":"Salvanou","sequence":"first","affiliation":[{"name":"Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8592-0380","authenticated-orcid":false,"given":"Argiris","family":"Kolokithas-Ntoukas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-8932","authenticated-orcid":false,"given":"Danai","family":"Prokopiou","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-3105","authenticated-orcid":false,"given":"Maria","family":"Theodosiou","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-7881","authenticated-orcid":false,"given":"Eleni","family":"Efthimiadou","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0471-6949","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Ko\u017ami\u0144ski","sequence":"additional","affiliation":[{"name":"Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-0806","authenticated-orcid":false,"given":"Stavros","family":"Xanthopoulos","sequence":"additional","affiliation":[{"name":"Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-8118","authenticated-orcid":false,"given":"Konstantinos","family":"Avgoustakis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6778-2201","authenticated-orcid":false,"given":"Penelope","family":"Bouziotis","sequence":"additional","affiliation":[{"name":"Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s41181-023-00211-5","article-title":"Novel Radionuclides for Use in Nuclear Medicine in Europe: Where Do We Stand and Where Do We Go?","volume":"8","author":"Radzina","year":"2023","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sharma, S., and Pandey, M.K. (2023). Radiometals in Imaging and Therapy: Highlighting Two Decades of Research. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101460"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1218670","DOI":"10.3389\/fchem.2023.1218670","article-title":"Developments in 177Lu-Based Radiopharmaceutical Therapy and Dosimetry","volume":"11","author":"George","year":"2023","journal-title":"Front. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3322\/caac.21578","article-title":"Brachytherapy: An Overview for Clinicians","volume":"69","author":"Chargari","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ijrobp.2013.07.011","article-title":"Benefit of Adjuvant Brachytherapy Versus External Beam Radiation for Early Breast Cancer: Impact of Patient Stratification on Breast Preservation","volume":"88","author":"Smith","year":"2014","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.5114\/jcb.2017.72607","article-title":"Current Status of Brachytherapy in Cancer Treatment\u2014Short Overview","volume":"9","author":"Skowronek","year":"2017","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1021\/cbmi.3c00092","article-title":"Cancer Brachytherapy at the Nanoscale: An Emerging Paradigm","volume":"2","author":"Ghosh","year":"2024","journal-title":"Chem. Biomed. Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.3389\/fonc.2021.766407","article-title":"Recent Advances in Brachytherapy Using Radioactive Nanoparticles: An Alternative to Seed-Based Brachytherapy","volume":"11","author":"Seniwal","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s11671-021-03628-6","article-title":"Nanoparticles for Cancer Therapy: Current Progress and Challenges","volume":"16","author":"Gavas","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12645-023-00165-y","article-title":"Radiolabeled Nanomaterial for Cancer Diagnostics and Therapeutics: Principles and Concepts","volume":"14","author":"Goel","year":"2023","journal-title":"Cancer Nanotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"405102","DOI":"10.1088\/1361-6528\/ac7ac0","article-title":"90Y-CA\/SPIONs for Dual Magnetic Hyperthermia-Radionuclide Nanobrachytherapy of Solid Tumours","volume":"33","author":"Karageorgou","year":"2022","journal-title":"Nanotechnology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1701460","DOI":"10.1002\/adhm.201701460","article-title":"Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy","volume":"7","author":"Fortin","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stankovi\u0107, D., Radovi\u0107, M., Stankovi\u0107, A., Mirkovi\u0107, M., Vukadinovi\u0107, A., Mijovi\u0107, M., Milanovi\u0107, Z., Ognjanovi\u0107, M., Jankovi\u0107, D., and Anti\u0107, B. (2023). Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071943"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e6493458","DOI":"10.1155\/2022\/6493458","article-title":"Applications of Iron Oxide Nanoparticles against Breast Cancer","volume":"2022","author":"Hosseinkazemi","year":"2022","journal-title":"J. Nanomater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.addr.2020.06.025","article-title":"Cancer Therapy with Iron Oxide Nanoparticles: Agents of Thermal and Immune Therapies","volume":"163\u2013164","author":"Soetaert","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fonc.2019.00059","article-title":"Functionalized Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as Platform for the Targeted Multimodal Tumor Therapy","volume":"9","author":"Janko","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"230658","DOI":"10.1007\/s11706-023-0658-4","article-title":"Progress in Cancer Therapy with Functionalized Fe3O4 Nanomaterials","volume":"17","author":"Wang","year":"2023","journal-title":"Front. Mater. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s41181-022-00161-4","article-title":"Radiolabeled Nanomaterials for Biomedical Applications: Radiopharmacy in the Era of Nanotechnology","volume":"7","author":"Pijeira","year":"2022","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Salvanou, E.-A., Kolokithas-Ntoukas, A., Liolios, C., Xanthopoulos, S., Paravatou-Petsotas, M., Tsoukalas, C., Avgoustakis, K., and Bouziotis, P. (2022). Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents. Nanomaterials, 12.","DOI":"10.3390\/nano12142490"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/FPC.0b013e32833ffb56","article-title":"Doxorubicin Pathways: Pharmacodynamics and Adverse Effects","volume":"21","author":"Thorn","year":"2011","journal-title":"Pharmacogenet. Genom."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wasiak, I., Kulikowska, A., Janczewska, M., Michalak, M., Cymerman, I.A., Nagalski, A., Kallinger, P., Szymanski, W.W., and Ciach, T. (2016). Dextran Nanoparticle Synthesis and Properties. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146237"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.tranon.2014.07.003","article-title":"Co-Encapsulation of Doxorubicin With Galactoxyloglucan Nanoparticles for Intracellular Tumor-Targeted Delivery in Murine Ascites and Solid Tumors","volume":"7","author":"Joseph","year":"2014","journal-title":"Transl. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dragojevic, S., Turner, L., and Raucher, D. (2022). Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042301"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Theodosiou, M., Boukos, N., Sakellis, E., Zachariadis, M., and Efthimiadou, E.K. (2019). Gold Nanoparticle Decorated pH-Sensitive Polymeric Nanocontainers as a Potential Theranostic Agent. Colloids Surf. B Biointerfaces, 183.","DOI":"10.1016\/j.colsurfb.2019.110420"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jsps.2015.02.014","article-title":"Remote Loading of Doxorubicin into Liposomes by Transmembrane pH Gradient to Reduce Toxicity toward H9c2 Cells","volume":"24","author":"Alyane","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3389\/fchem.2018.00224","article-title":"A Novel Metal-Based Imaging Probe for Targeted Dual-Modality SPECT\/MR Imaging of Angiogenesis","volume":"6","author":"Tsoukalas","year":"2018","journal-title":"Front. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2015.02.002","article-title":"Preparation of Multi-Functionalized Fe3O4\/Au Nanoparticles for Medical Purposes","volume":"128","author":"Viota","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biomaterials.2016.03.015","article-title":"Synthesis and Evaluation of Condensed Magnetic Nanocrystal Clusters with in Vivo Multispectral Optoacoustic Tomography for Tumour Targeting","volume":"91","author":"Sarigiannis","year":"2016","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1021\/cm404053v","article-title":"Theranostics of Epitaxially Condensed Colloidal Nanocrystal Clusters, through a Soft Biomineralization Route","volume":"26","author":"Zoppellaro","year":"2014","journal-title":"Chem. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/smll.201102525","article-title":"Merging High Doxorubicin Loading with Pronounced Magnetic Response and Bio-Repellent Properties in Hybrid Drug Nanocarriers","volume":"8","author":"Bakandritsos","year":"2012","journal-title":"Small"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11292","DOI":"10.1038\/s41598-020-68017-y","article-title":"Doxorubicin-Loaded Iron Oxide Nanoparticles for Glioblastoma Therapy: A Combinational Approach for Enhanced Delivery of Nanoparticles","volume":"10","author":"Norouzi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nieciecka, D., Celej, J., \u017buk, M., Majkowska-Pilip, A., \u017belechowska-Matysiak, K., Lis, A., and Osial, M. (2021). Hybrid System for Local Drug Delivery and Magnetic Hyperthermia Based on SPIONs Loaded with Doxorubicin and Epirubicin. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040480"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1021\/acsapm.0c00433","article-title":"Unexpected Plasticization Effects on the Structure and Properties of Polyelectrolyte Complexed Chitosan\/Alginate Materials","volume":"2","author":"Chen","year":"2020","journal-title":"ACS Appl. Polym. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42120","DOI":"10.1039\/D0RA08699A","article-title":"Effect of Molecular Weight of Polyethylene Glycol on Crystallization Behaviors, Thermal Properties and Tensile Performance of Polylactic Acid Stereocomplexes","volume":"10","author":"Li","year":"2020","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"780171","DOI":"10.1155\/2010\/780171","article-title":"Controlled Release of Doxorubicin from Doxorubicin\/\u03b3-Polyglutamic Acid Ionic Complex","volume":"2010","author":"Manocha","year":"2010","journal-title":"J. Nanomater."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Singh, N., Sallem, F., Mirjolet, C., Nury, T., Sahoo, S.K., Millot, N., and Kumar, R. (2019). Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment. Nanomaterials, 9.","DOI":"10.3390\/nano9020138"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s11051-012-0977-3","article-title":"Quantitative Characterization of Nanoparticle Agglomeration within Biological Media","volume":"14","author":"Hondow","year":"2012","journal-title":"J. Nanoparticle Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1155\/2013\/313081","article-title":"Detection Limits of DLS and UV-Vis Spectroscopy in Characterization of Polydisperse Nanoparticles Colloids","volume":"2013","author":"Tomaszewska","year":"2013","journal-title":"J. Nanomater."},{"key":"ref_39","unstructured":"(2023, August 07). DLS and Zeta Potential\u2014What They Are and What They Are Not?\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/27297779\/."},{"key":"ref_40","unstructured":"(2023, August 16). Determination of Isoelectric Points and Relative Charge Variants of 23 Therapeutic Monoclonal Antibodies\u2014ScienceDirect. Available online: https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S1570023217313880?via%3Dihub."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.1038\/s41598-017-03959-4","article-title":"A New Paradigm for Antiangiogenic Therapy through Controlled Release of Bevacizumab from PLGA Nanoparticles","volume":"7","author":"Sousa","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Oltolina, F., Colangelo, D., Miletto, I., Clemente, N., Miola, M., Vern\u00e9, E., Prat, M., and Follenzi, A. (2019). Tumor Targeting by Monoclonal Antibody-functionalized Magnetic Nanoparticles. Nanomaterials, 9.","DOI":"10.3390\/nano9111575"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-physiol-021119-034627","article-title":"The Acidic Tumor Microenvironment as a Driver of Cancer","volume":"82","author":"Boedtkjer","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22214","DOI":"10.1021\/acsomega.9b03594","article-title":"Folic Acid-Functionalized, Condensed Magnetic Nanoparticles for Targeted Delivery of Doxorubicin to Tumor Cancer Cells Overexpressing the Folate Receptor","volume":"4","author":"Angelopoulou","year":"2019","journal-title":"ACS Omega"},{"key":"ref_45","first-page":"369","article-title":"Characterization of Bevacizumab by Dynamic Light Scattering While Maintaining Its Native Structure","volume":"37","author":"Akbas","year":"2018","journal-title":"Pharmazie"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejps.2017.05.019","article-title":"Biophysical Study of Bevacizumab Structure and Bioactivity under Thermal and pH-Stresses","volume":"105","author":"Sousa","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2174\/1389201015666140619120834","article-title":"Quantification, Microbial Contamination, Physico-Chemical Stability of Repackaged Bevacizumab Stored Under Different Conditions","volume":"15","author":"Signorello","year":"2014","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1053\/j.semnuclmed.2008.05.002","article-title":"Therapeutic Radionuclides: Biophysical and Radiobiologic Principles","volume":"38","author":"Kassis","year":"2008","journal-title":"Semin. Nucl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109766","DOI":"10.1016\/j.msec.2019.109766","article-title":"Preparation and in Vitro Evaluation of Radiolabeled HA-PLGA Nanoparticles as Novel MTX Delivery System for Local Treatment of Rheumatoid Arthritis","volume":"103","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s00259-019-04345-0","article-title":"Terbium-161 for PSMA-Targeted Radionuclide Therapy of Prostate Cancer","volume":"46","author":"Umbricht","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1475-2867-13-94","article-title":"Tumor Cell Response to Bevacizumab Single Agent Therapy in Vitro","volume":"13","author":"Hein","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_52","first-page":"627","article-title":"Combination Therapy of cRGD-DOX Self-Assembled Nanoparticles and Bevacizumab for Breast Cancer","volume":"28","author":"Wang","year":"2019","journal-title":"J. Chin. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/nrc3627","article-title":"VEGF Targets the Tumour Cell","volume":"13","author":"Goel","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1021\/bc100261d","article-title":"Effects of Charge on Antibody Tissue Distribution and Pharmacokinetics","volume":"21","author":"Boswell","year":"2010","journal-title":"Bioconjug. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.4161\/mabs.29809","article-title":"Framework Selection Can Influence Pharmacokinetics of a Humanized Therapeutic Antibody through Differences in Molecule Charge","volume":"6","author":"Li","year":"2014","journal-title":"mAbs"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/protein\/gzq009","article-title":"Reduced Elimination of IgG Antibodies by Engineering the Variable Region","volume":"23","author":"Igawa","year":"2010","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.msec.2016.09.016","article-title":"Preferential Binding of Positive Nanoparticles on Cell Membranes Is Due to Electrostatic Interactions: A Too Simplistic Explanation That Does Not Take into Account the Nanoparticle Protein Corona","volume":"70","author":"Forest","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101692","DOI":"10.1016\/j.mtcomm.2020.101692","article-title":"Cellular Uptake and Retention of Nanoparticles: Insights on Particle Properties and Interaction with Cellular Components","volume":"25","author":"Augustine","year":"2020","journal-title":"Mater. Today Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1039\/C8BM00225H","article-title":"Bevacizumab and Near Infrared Probe Conjugated Iron Oxide Nanoparticles for Vascular Endothelial Growth Factor Targeted MR and Optical Imaging","volume":"6","author":"Lin","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s00259-006-0099-1","article-title":"In Vivo Tumor Angiogenesis Imaging with Site-Specific Labeled 99mTc-HYNIC-VEGF","volume":"33","author":"Blankenberg","year":"2006","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"(2023, August 04). Vascular Endothelial Growth Factor Selectively Targets Boronated Dendrimers to Tumor Vasculature|Molecular Cancer Therapeutics|American Association for Cancer Research. Available online: https:\/\/aacrjournals.org\/mct\/article\/4\/9\/1423\/235607\/Vascular-endothelial-growth-factor-selectively.","DOI":"10.1158\/1535-7163.MCT-05-0161"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.2147\/IJN.S415063","article-title":"In Vivo Biodistribution and Clearance of Magnetic Iron Oxide Nanoparticles for Medical Applications","volume":"18","author":"Machnicka","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"C\u0119drowska, E., Pruszy\u0144ski, M., Gaw\u0119da, W., \u017buk, M., Krysi\u0144ski, P., Bruchertseifer, F., Morgenstern, A., Karageorgou, M.-A., Bouziotis, P., and Bilewicz, A. (2020). Trastuzumab Conjugated Superparamagnetic Iron Oxide Nanoparticles Labeled with 225Ac as a Perspective Tool for Combined \u03b1-Radioimmunotherapy and Magnetic Hyperthermia of HER2-Positive Breast Cancer. Molecules, 25.","DOI":"10.3390\/molecules25051025"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1021\/acs.biomac.5b01642","article-title":"Stability and Biodistribution of Thiol-Functionalized and 177Lu-Labeled Metal Chelating Polymers Bound to Gold Nanoparticles","volume":"17","author":"Yook","year":"2016","journal-title":"Biomacromolecules"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Leonte, R.A., Chilug, L.E., \u0218erban, R., Must\u0103ciosu, C., Raicu, A., Manda, G., and Niculae, D. (2021). Preparation and Preliminary Evaluation of Neurotensin Radiolabelled with 68Ga and 177Lu as Potential Theranostic Agent for Colon Cancer. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040506"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"753","DOI":"10.4161\/mabs.22189","article-title":"A Strategy for Risk Mitigation of Antibodies with Fast Clearance","volume":"4","author":"Theil","year":"2012","journal-title":"mAbs"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2217\/nnm-2016-0316","article-title":"Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy","volume":"12","author":"Zhu","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1007\/s11095-010-0360-y","article-title":"Intratumoral Drug Delivery with Nanoparticulate Carriers","volume":"28","author":"Holback","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Salvanou, E.-A., Stellas, D., Tsoukalas, C., Mavroidi, B., Paravatou-Petsotas, M., Kalogeropoulos, N., Xanthopoulos, S., Denat, F., Laurent, G., and Bazzi, R. (2020). A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020188"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.1021\/acs.molpharmaceut.3c00414","article-title":"Improvement of the Effectiveness of HER2+Cancer Therapy by Use of Doxorubicin and Trastuzumab Modified Radioactive Gold Nanoparticles","volume":"20","author":"Salvanou","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1021\/acsanm.0c01427","article-title":"177Lu-Labeled Eu-Doped Mesoporous SiO2 Nanoparticles as a Theranostic Radiopharmaceutical for Colorectal Cancer","volume":"3","author":"Viana","year":"2020","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_72","unstructured":"(2023, August 20). EMA EndolucinBeta. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/endolucinbeta."},{"key":"ref_73","unstructured":"Department of Health, Therapeutic Goods Administration (2022). Australian Public Assessment Report for Lutetium (177Lu) Chloride."},{"key":"ref_74","unstructured":"Straus, S., and Huber, M. (2023, January 31). Pharmacovigilance Risk Assessment Committee (PRAC). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/minutes\/minutes-prac-meeting-2-5-may-2022_en.pdf."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kato, H., Huang, X., Kadonaga, Y., Katayama, D., Ooe, K., Shimoyama, A., Kabayama, K., Toyoshima, A., Shinohara, A., and Hatazawa, J. (2021). Intratumoral Administration of Astatine-211-Labeled Gold Nanoparticle for Alpha Therapy. J. Nanobiotechnology, 19.","DOI":"10.1186\/s12951-021-00963-9"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.nano.2009.11.001","article-title":"Radioactive Gold Nanoparticles in Cancer Therapy: Therapeutic Efficacy Studies of GA-198AuNP Nanoconstruct in Prostate Tumor\u2013Bearing Mice","volume":"6","author":"Chanda","year":"2010","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"12426","DOI":"10.1073\/pnas.1121174109","article-title":"Laminin Receptor Specific Therapeutic Gold Nanoparticles (198AuNP-EGCg) Show Efficacy in Treating Prostate Cancer","volume":"109","author":"Shukla","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14561","DOI":"10.1039\/C7DT00383H","article-title":"Mangiferin Functionalized Radioactive Gold Nanoparticles (MGF-198AuNPs) in Prostate Tumor Therapy: Green Nanotechnology for Production, in Vivo Tumor Retention and Evaluation of Therapeutic Efficacy","volume":"46","author":"Khoobchandani","year":"2017","journal-title":"Dalton Trans."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"862","DOI":"10.2174\/1381612825666190306164157","article-title":"Evaluation of Local Injection of Bevacizumab against Triple-Negative Breast Cancer Xenograft Tumors","volume":"25","author":"Jiang","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"119628","DOI":"10.1016\/j.ijpharm.2020.119628","article-title":"Aminosilanized Flower-Structured Superparamagnetic Iron Oxide Nanoparticles Coupled to 131I-Labeled CC49 Antibody for Combined Radionuclide and Hyperthermia Therapy of Cancer","volume":"587","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"936","DOI":"10.2967\/jnumed.115.168906","article-title":"Intratumorally Injected 177 Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer","volume":"57","author":"Yook","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tao, K., Fang, M., Alroy, J., and Sahagian, G.G. (2008). Imagable 4T1 Model for the Study of Late Stage Breast Cancer. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-228"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10555-007-9094-7","article-title":"Tumour Vascularization: Sprouting Angiogenesis and Beyond","volume":"26","author":"Hillen","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/vhrm.2006.2.3.213","article-title":"Angiogenesis in Cancer","volume":"2","author":"Nishida","year":"2006","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.2967\/jnumed.119.236265","article-title":"177Lu-NM600 Targeted Radionuclide Therapy Extends Survival in Syngeneic Murine Models of Triple-Negative Breast Cancer","volume":"61","author":"Hernandez","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Varan, G., Varan, C., \u00d6zt\u00fcrk, S.C., Benito, J.M., Esenda\u011fl\u0131, G., and Bilensoy, E. (2021). Therapeutic Efficacy and Biodistribution of Paclitaxel-Bound Amphiphilic Cyclodextrin Nanoparticles: Analyses in 3D Tumor Culture and Tumor-Bearing Animals In Vivo. Nanomaterials, 11.","DOI":"10.3390\/nano11020515"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ao, H., Wang, Z., Lu, L., Ma, H., Li, H., Fu, J., Li, M., Han, M., Guo, Y., and Wang, X. (2022). Enhanced Tumor Accumulation and Therapeutic Efficacy of Liposomal Drugs through Over-Threshold Dosing. J. Nanobiotechnology, 20.","DOI":"10.1186\/s12951-022-01349-1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7677","DOI":"10.1158\/1078-0432.CCR-04-1443","article-title":"Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy","volume":"10","author":"Lu","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/bs.mie.2019.02.023","article-title":"Selection and Optimization of Enzyme Reporters for Chemical Cytometry","volume":"Volume 622","author":"Shukla","year":"2019","journal-title":"Methods in Enzymology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/j.1349-7006.1999.tb00844.x","article-title":"Expression of Vascular Endothelial Growth Factor (VEGF) Family Members in Breast Cancer","volume":"90","author":"Kurebayashi","year":"1999","journal-title":"Jpn. J. Cancer Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/5\/1030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:05:56Z","timestamp":1760105156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/5\/1030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":90,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["molecules29051030"],"URL":"https:\/\/doi.org\/10.3390\/molecules29051030","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]}}}