{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:29:26Z","timestamp":1772461766185,"version":"3.50.1"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-24-00601"],"award-info":[{"award-number":["23-24-00601"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cancer-related deaths primarily occur due to metastasis, a process involving the migration and invasion of cancer cells. In most solid tumors, metastasis occurs through collective cell migration (CCM), guided by \u201ccellular leaders\u201d. These leader cells generate forces through actomyosin-mediated protrusion and contractility. The cytoskeletal mechanisms employed by metastatic cells during the migration process closely resemble the use of the actin cytoskeleton in endocytosis. In our previous work, we revealed that tumor cells exhibiting high metastatic potential (MP) are more adept at encapsulating 100\u2013200 nm nanoparticles than those with lower MP. The objective of this study was to investigate whether nanoparticle encapsulation could effectively differentiate leader tumor cells during their CCM. To achieve our objectives, we employed a two-dimensional CCM model grounded in the wound-healing (\u201cscratch\u201d) assay, utilizing two breast cancer cell lines, MCF7 and MDA-MB-231, which display low and high migratory potential, respectively. We conducted calibration experiments to identify the \u201coptimal time\u201d at which cells exhibit peak speed during wound closure. Furthermore, we carried out experiments to assess nanoparticle uptake, calculating the colocalization coefficient, and employed phalloidin staining to analyze the anisotropy and orientation of actin filaments. The highest activity for low-MP cells was achieved at 2.6 h during the calibration experiments, whereas high-MP cells were maximally active at 3.9 h, resulting in 8% and 11% reductions in wound area, respectively. We observed a significant difference in encapsulation efficiency between leader and peripheral cells for both high-MP (p &lt; 0.013) and low-MP (p &lt; 0.02) cells. Moreover, leader cells demonstrated a considerably higher anisotropy coefficient (p &lt; 0.029), indicating a more organized, directional structure of actin filaments compared to peripheral cells. Thus, nanoparticle encapsulation offers a groundbreaking approach to identifying the most aggressive and invasive leader cells during the CCM process in breast cancer. Detecting these cells is crucial for developing targeted therapies that can effectively curb metastasis and improve patient outcomes.<\/jats:p>","DOI":"10.3390\/life15010127","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:04:12Z","timestamp":1737345852000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Navigating the Collective: Nanoparticle-Assisted Identification of Leader Cancer Cells During Migration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9825-8466","authenticated-orcid":false,"given":"Anastasia","family":"Alexandrova","sequence":"first","affiliation":[{"name":"The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5403-6916","authenticated-orcid":false,"given":"Elizaveta","family":"Kontareva","sequence":"additional","affiliation":[{"name":"The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Pustovalova","sequence":"additional","affiliation":[{"name":"The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3425-723X","authenticated-orcid":false,"given":"Sergey","family":"Leonov","sequence":"additional","affiliation":[{"name":"The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia"},{"name":"Institute of Cell Biophysics of Russian Academy of Sciences, Pushchino 142290, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-5609","authenticated-orcid":false,"given":"Yulia","family":"Merkher","sequence":"additional","affiliation":[{"name":"The Laboratory of Personalized Chemo-Radiation Therapy, Institute of Future Biophysics, Moscow 141700, Russia"},{"name":"Faculty of Biomedical Engineering, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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