Neutrophil-mediated transport is crucial for short-circulating magnetic nanoparticles delivery to tumorsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 апреля 2020 г.
Аннотация:Recently neutrophil-based nanoparticles (NPs) drug delivery systems have gained considerable attention in cancer therapy. Numerous studies have been conducted to identify optimal NPs parameters for passive tumor targeting, while there is a fundamental dearth of knowledge about the factors governing cell-mediated delivery. Here, using intravital microscopy and magnetic resonance imaging we describe accumulation dynamics of 140 nm magnetic cubes and clusters in murine breast cancer (4T1) and colon cancer (CT26) models. Notwithstanding rapid clearance from the blood flow, NPs readily accumulated in tumors at later time points. Both NPs types were captured mostly by intravascular neutrophils immediately after injection and transmigration of NPs -bound neutrophils through the vessel wall was first shown in real-time. A dramatic drop in NPs accumulation upon Ly6G and Gr1 depletion further confirmed neutrophils role as a biocarrier for targeting tumors. Of note, for shorter circulating NPs a cell-dependent delivery route was more impactful, while the accumulation of longer circulating counterpart was less compromised by neutrophil depletion. Neutrophil-mediated transport was also shown to depend on tumor type being more efficient in neutrophil-rich tumors. Revealing NPs characteristics and host factors influencing the neutrophil-based tumor targeting will help to rationally design drug delivery systems for improved cancer treatment.