{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:49Z","timestamp":1787029069753,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for Science and Technology\/Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACyT, Mexico)","award":["SEP-CONACyT-CB-2016-01-287217"],"award-info":[{"award-number":["SEP-CONACyT-CB-2016-01-287217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Reconstituted high-density lipoproteins (rHDLs) can transport and specifically release drugs and imaging agents, mediated by the Scavenger Receptor Type B1 (SR-B1) present in a wide variety of tumor cells, providing convenient platforms for developing theranostic systems. Usually, phospholipids or Apo-A1 lipoproteins on the particle surfaces are the motifs used to conjugate molecules for the multifunctional purposes of the rHDL nanoparticles. Cholesterol has been less addressed as a region to bind molecules or functional groups to the rHDL surface. To maximize the efficacy and improve the radiolabeling of rHDL theranostic systems, we synthesized compounds with bifunctional agents covalently linked to cholesterol. This strategy means that the radionuclide was bound to the surface, while the therapeutic agent was encapsulated in the lipophilic core. In this research, HYNIC-S-(CH2)3-S-Cholesterol and DOTA-benzene-p-SC-NH-(CH2)2-NH-Cholesterol derivatives were synthesized to prepare nanoparticles (NPs) of HYNIC-rHDL and DOTA-rHDL, which can subsequently be linked to radionuclides for SPECT\/PET imaging or targeted radiotherapy. HYNIC is used to complexing 99mTc and DOTA for labeling molecules with 111, 113mIn, 67, 68Ga, 177Lu, 161Tb, 225Ac, and 64Cu, among others. In vitro studies showed that the NPs of HYNIC-rHDL and DOTA-rHDL maintain specific recognition by SR-B1 and the ability to internalize and release, in the cytosol of cancer cells, the molecules carried in their core. The biodistribution in mice showed a similar behavior between rHDL (without surface modification) and HYNIC-rHDL, while DOTA-rHDL exhibited a different biodistribution pattern due to the significant reduction in the lipophilicity of the modified cholesterol molecule. Both systems demonstrated characteristics for the development of suitable theranostic platforms for personalized cancer treatment.<\/jats:p>","DOI":"10.3390\/molecules27207046","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T22:19:53Z","timestamp":1666217993000},"page":"7046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Engineered rHDL Nanoparticles as a Suitable Platform for Theranostic Applications"],"prefix":"10.3390","volume":"27","author":[{"given":"Liliana","family":"Aranda-Lara","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-3811","authenticated-orcid":false,"given":"Keila","family":"Isaac-Oliv\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Estado de M\u00e9xico, 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, Estado de M\u00e9xico, 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, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Gonz\u00e1lez-Romero","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50120, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Mercado-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50120, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Garc\u00eda-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50120, Estado de M\u00e9xico, 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, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Estrada","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-6791","authenticated-orcid":false,"given":"Enrique","family":"Morales-Avila","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50120, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.addr.2016.04.020","article-title":"Lipoproteins and Lipoprotein Mimetics for Imaging and Drug Delivery","volume":"106","author":"Thaxton","year":"2016","journal-title":"Adv. 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