Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment.

Autor: Zelepukin IV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia. zelepukin@phystech.edu.; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409, Moscow, Russia. zelepukin@phystech.edu., Griaznova OY; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia.; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409, Moscow, Russia., Shevchenko KG; Institute of Cytology of the Russian Academy of Sciences, 194064, Saint Petersburg, Russia.; Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences, 108819, Moscow, Russia., Ivanov AV; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia., Baidyuk EV; Institute of Cytology of the Russian Academy of Sciences, 194064, Saint Petersburg, Russia., Serejnikova NB; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia., Volovetskiy AB; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia., Deyev SM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia. deyev@ibch.ru.; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409, Moscow, Russia. deyev@ibch.ru.; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia. deyev@ibch.ru., Zvyagin AV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia. andrei.zvyagin@mq.edu.au.; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409, Moscow, Russia. andrei.zvyagin@mq.edu.au.; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia. andrei.zvyagin@mq.edu.au.; MQ Photonics Centre, Macquarie University, 2109, Sydney, Australia. andrei.zvyagin@mq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 14; Vol. 13 (1), pp. 6910. Date of Electronic Publication: 2022 Nov 14.
DOI: 10.1038/s41467-022-34718-3
Abstrakt: Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.
(© 2022. The Author(s).)
Databáze: MEDLINE
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