{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:03:52Z","timestamp":1787997832513,"version":"build-2784847793"},"reference-count":53,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["18-29-09022\\20"],"award-info":[{"award-number":["18-29-09022\\20"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian Federation President\u2019s scholarship 2022-2023","award":["SP-3848.2022.4"],"award-info":[{"award-number":["SP-3848.2022.4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety\u2014alpha-fetoprotein receptor-binding peptide\u2014enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors.<\/jats:p>","DOI":"10.3390\/ijms23063119","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:06:10Z","timestamp":1647313570000},"page":"3119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3361-9136","authenticated-orcid":false,"given":"Nikita","family":"Yabbarov","sequence":"first","affiliation":[{"name":"N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-3117","authenticated-orcid":false,"given":"Elena","family":"Nikolskaya","sequence":"additional","affiliation":[{"name":"N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sokol","sequence":"additional","affiliation":[{"name":"N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9999-4652","authenticated-orcid":false,"given":"Mariia","family":"Mollaeva","sequence":"additional","affiliation":[{"name":"N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Chirkina","sequence":"additional","affiliation":[{"name":"N. M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Seregina","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-2484","authenticated-orcid":false,"given":"Mikhail","family":"Gulyaev","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Medicine, Lomonosov Moscow State University, 117192 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Pirogov","sequence":"additional","affiliation":[{"name":"Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rem","family":"Petrov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.msec.2018.11.001","article-title":"Thinking small, doing big: Current success and future trends in drug delivery systems for improving cancer therapy with special focus on liver cancer","volume":"95","author":"Limeres","year":"2019","journal-title":"Mater. 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