Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission

Shipunova, V.O.; Belova, M.M.; Kotelnikova, P.A.; Shilova, O.N.; Mirkasymov, A.B.; Danilova, N.V.; Komedchikova, E.N.; Popovtzer, R.; Deyev, S.M.; Nikitin, M.P.

Авторы: Shipunova Victoria O., Belova Mariia M., Kotelnikova Polina A., Shilova Olga N., Mirkasymov Aziz B., Danilova Natalia V., Komedchikova Elena N., Popovtzer Rachela, Deyev Sergey M., Nikitin Maxim P.
Журнал: Pharmaceutics
Том: 14
Номер: 5
Год издания: 2022
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Номер статьи: 1013
DOI: 10.3390/pharmaceutics14051013
Аннотация: Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are prom-ising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated. Here we show targeted photothermal therapy of solid tumors with 35 nm HER2-targeted Ag NPs, which were produced by the green synthesis using an aqueous extract of Lavandula angustifolia Mill. Light ir-radiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °С in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold poly-peptide, affibody ZHER2:342, which recognizes a clinically relevant oncomarker HER2. The conjuga-tion was mediated by the PEG linker to obtain Ag-PEG-HER2 nanoparticles. Flow cytometry tests showed that Ag-PEG-HER2 particles successfully bind to HER2-overexpressing cells with a speci-ficity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed effi-cient internalization of Ag-PEG-HER2 into cells in less than 2 h of incubation. Cytotoxicity assays demonstrated effective cell death upon exposure to Ag-PEG-HER2 and irradiation, caused by the production of reactive oxygen species. Xenograft tumor therapy with Ag-PEG-HER2 particles in vivo resulted in full primary tumor regression and the prevention of metastatic spread. Thus, for the first time, we have shown that HER2-directed plasmonic Ag nanoparticles are effective sensi-tizers for targeted photothermal oncotherapy.
Добавил в систему: Данилова Наталья Владимировна

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