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
Department of Nanobiomedicine, Sirius University of Science and Technology, 1 Olympic Ave., 354340 Sochi, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., 117997 Moscow, Russia.
Pharmaceutics. 2022 May 8;14(5):1013. doi: 10.3390/pharmaceutics14051013.
Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising 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 Mill. Light irradiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °C in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold polypeptide, affibody Z, which recognizes a clinically relevant oncomarker HER2. The conjugation 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 specificity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed efficient 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 sensitizers for targeted photothermal oncotherapy.
表现出局域表面等离子体共振（LSPR）现象的纳米颗粒是用于诊断和癌症治疗的有前途的工具。在广泛使用的金属纳米颗粒中，银纳米颗粒（Ag NPs）具有最强的光散射和表面等离子体强度。然而，迄今为止，Ag NPs的治疗潜力一直被低估。在这里，我们展示了用35纳米的HER2靶向Ag NPs对实体瘤进行靶向光热治疗，这些纳米颗粒是通过使用 Mill的水提取物进行绿色合成制备的。光照射测试证明了这些纳米颗粒具有有效的热疗特性，即在10分钟内升温10°C。为了介导靶向癌症治疗，将Ag NPs与支架多肽亲和体Z偶联，亲和体Z可识别临床上相关的肿瘤标志物HER2。通过聚乙二醇（PEG）接头介导偶联，以获得Ag-PEG-HER2纳米颗粒。流式细胞术测试表明，Ag-PEG-HER2颗粒成功地与HER2过表达细胞结合，其特异性与全尺寸抗HER2免疫球蛋白相当。共聚焦显微镜研究表明，在孵育不到2小时的时间内，Ag-PEG-HER2能有效地内化到细胞中。细胞毒性试验表明，暴露于Ag-PEG-HER2并进行照射后，由于活性氧的产生导致细胞有效死亡。体内用Ag-PEG-HER2颗粒进行异种移植肿瘤治疗导致原发性肿瘤完全消退并防止转移扩散。因此，我们首次表明，HER2导向的等离子体Ag纳米颗粒是靶向光热肿瘤治疗的有效增敏剂。
