Mild hyperthermia induced by gold nanorods acts as a dual-edge blade in the fate of SH-SY5Y cells via autophagy

Maryam Ghafarkhani,Amir Zarebkohan,Majid Sadeghizadeh,Abbas Karimi,Cigir Biray Avci,Farhad Bani,Reza Rahbarghazi

doi:10.1038/s41598-021-02697-y

Maryam Ghafarkhani, Amir Zarebkohan + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-02697-y

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Abstract

Unraveling unwanted side effects of nanotechnology-based therapies like photothermal therapy (PTT) is vital in translational nanomedicine. Herein, we monitored the relationship between autophagic response at the transcriptional level by using a PCR array and tumor formation ability by colony formation assay in the human neuroblastoma cell line, SH-SY5Y, 48 h after being exposed to two different mild hyperthermia (43 and 48 °C) induced by PTT. In this regard, the promotion of apoptosis and autophagy were evaluated using immunofluorescence imaging and flow cytometry analyses. Protein levels of Ki-67, P62, and LC3 were measured using ELISA. Our results showed that of 86 genes associated with autophagy, the expression of 54 genes was changed in response to PTT. Also, we showed that chaperone-mediated autophagy (CMA) and macroautophagy are stimulated in PTT. Importantly, the results of this study also showed significant changes in genes related to the crosstalk between autophagy, dormancy, and metastatic activity of treated cells. Our findings illustrated that PTT enhances the aggressiveness of cancer cells at 43 °C, in contrast to 48 °C by the regulation of autophagy-dependent manner.

Highlights

Unraveling unwanted side effects of nanotechnology-based therapies like photothermal therapy (PTT) is vital in translational nanomedicine
We investigated the modulation of autophagy response and its final effects on tumorigenesis ability in human neuroblastoma cell line SH-SY5Y after exposure to lower and higher temperatures produced by albumincoated gold nanorods (AuNRs)-mediated PTT
BSA molecules were efficiently attached to the surface of AuNRs, which was indicated by the redshift of the plasmon peak of AuNRs in the UV–Vis spectrum (Fig. 2B), and the change of surface charge analyzed by dynamic light scattering (DLS) (Fig. 2D)

Summary

Introduction

Unraveling unwanted side effects of nanotechnology-based therapies like photothermal therapy (PTT) is vital in translational nanomedicine. Nano-bio interactions and biological consequences of using nanotechnology-based therapies have been considered a hot topic in the recent decay because of its importance in the bench to bedside translation Considering various advantages such as noninvasive entity, short treatment schedule, lower side effects to healthy cells, and high efficiency compared to chemo/radiotherapy, PTT has attracted immense interest in cancer therapy[1,2,3]. Sudden release of large amounts of growth/proinflammatory factors following necrotic death increases the risk of exacerbating the aggressiveness and metastatic capability of the remaining cancer cells[5,17] Commensurate with these comments, researchers have focused on mild hyperthermia (43–48 °C) induced by PTT, to avoid such r isks[18,19,20]. Yujuan and Scientific Reports | (2021) 11:23984

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