{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:38:22Z","timestamp":1790642302815,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T00:00:00Z","timestamp":1648339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB2017-2018-A1-S-36841"],"award-info":[{"award-number":["CB2017-2018-A1-S-36841"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Actinium-225 and other alpha-particle-emitting radionuclides have shown high potential for cancer treatment. Reconstituted high-density lipoproteins (rHDL) specifically recognize the scavenger receptor B type I (SR-BI) overexpressed in several types of cancer cells. Furthermore, after rHDL-SR-BI recognition, the rHDL content is injected into the cell cytoplasm. This research aimed to prepare a targeted 225Ac-delivering nanosystem by encapsulating the radionuclide into rHDL nanoparticles. The synthesis of rHDL was performed in two steps using the microfluidic synthesis method for the subsequent encapsulation of 225Ac, previously complexed to a lipophilic molecule (225Ac-DOTA-benzene-p-SCN, CLog P = 3.42). The nanosystem (13 nm particle size) showed a radiochemical purity higher than 99% and stability in human serum. In vitro studies in HEP-G2 and PC-3 cancer cells (SR-BI positive) demonstrated that 225Ac was successfully internalized into the cytoplasm of cells, delivering high radiation doses to cell nuclei (107 Gy to PC-3 and 161 Gy to HEP-G2 nuclei at 24 h), resulting in a significant decrease in cell viability down to 3.22 \u00b1 0.72% for the PC-3 and to 1.79 \u00b1 0.23% for HEP-G2 at 192 h after 225Ac-rHDL treatment. After intratumoral 225Ac-rHDL administration in mice bearing HEP-G2 tumors, the biokinetic profile showed significant retention of radioactivity in the tumor masses (90.16 \u00b1 2.52% of the injected activity), which generated ablative radiation doses (649 Gy\/MBq). The results demonstrated adequate properties of rHDL as a stable carrier for selective deposition of 225Ac within cancer cells overexpressing SR-BI. The results obtained in this research justify further preclinical studies, designed to evaluate the therapeutic efficacy of the 225Ac-rHDL system for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor.<\/jats:p>","DOI":"10.3390\/molecules27072156","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:29:36Z","timestamp":1648416576000},"page":"2156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["225Ac-rHDL Nanoparticles: A Potential Agent for Targeted Alpha-Particle Therapy of Tumors Overexpressing SR-BI Proteins"],"prefix":"10.3390","volume":"27","author":[{"given":"Tania","family":"Hern\u00e1ndez-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"},{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-7605","authenticated-orcid":false,"given":"Guillermina","family":"Ferro-Flores","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-6791","authenticated-orcid":false,"given":"Enrique","family":"Morales-\u00c1vila","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keila","family":"Isaac-Oliv\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8412","authenticated-orcid":false,"given":"Blanca","family":"Ocampo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Aranda-Lara","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-1598","authenticated-orcid":false,"given":"Clara","family":"Santos-Cuevas","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-3816","authenticated-orcid":false,"given":"Myrna","family":"Luna-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0061-370X","authenticated-orcid":false,"given":"Laura","family":"De Nardo","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, University of Padua, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8386","authenticated-orcid":false,"given":"Antonio","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy"},{"name":"Veneto Institute of Oncology IOV-IRCCS, 35138 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-3616","authenticated-orcid":false,"given":"Laura","family":"Mel\u00e9ndez-Alafort","sequence":"additional","affiliation":[{"name":"Veneto Institute of Oncology IOV-IRCCS, 35138 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1016\/j.nano.2016.05.009","article-title":"Schwendeman, Evaluation of reconstituted high-density lipoprotein (rHDL) as a drug delivery platform\u2014A detailed survey of rHDL particles ranging from biophysical properties to clinical implications","volume":"12","author":"Simonsen","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3389\/fphar.2016.00466","article-title":"Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging","volume":"7","author":"Mooberry","year":"2016","journal-title":"Front. 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