Photothermal effect of albumin-modified gold nanorods diminished neuroblastoma cancer stem cells dynamic growth by modulating autophagy

Küçük Resim Yok

Tarih

2022

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Nature Portfolio

Erişim Hakkı

info:eu-repo/semantics/openAccess

Özet

Here, we investigated the photothermal effect of gold nanorods (GNRs) on human neuroblastoma CD133(+) cancer stem cells (CSCs) via autophagic cell death. GNRs were synthesized using Cetyltrimethylammonium bromide (CTAB), covered with bovine serum albumin (BSA). CD133(+) CSCs were enriched from human neuroblastoma using the magnetic-activated cell sorting (MACS) technique. Cells were incubated with GNRs coated with BSA and exposed to 808-nm near-infrared laser irradiation for 8 min to yield low (43 degrees C), medium (46 degrees C), and high (49 degrees C) temperatures. After 24 h, the survival rate and the percent of apoptotic and necrotic CSCs were measured using MTT assay and flow cytometry. The expression of different autophagy-related genes was measured using polymerase chain reaction (PCR) array analysis. Protein levels of P62 and LC3 were detected using an enzyme-linked immunosorbent assay (ELISA). The viability of CSC was reduced in GNR-exposed cells compared to the control group (p < 0.05). At higher temperatures (49 degrees C), the percent of apoptotic CSCs, but not necrotic cells, increased compared to the lower temperatures. Levels of intracellular LC3 and P62 were reduced and increased respectively when the temperature increased to 49 degrees C (p < 0.05). These effects were non-significant at low and medium temperatures (43 and 46 degrees C) related to the control CSCs (p > 0.05). The clonogenic capacity of CSC was also inhibited after photothermal therapy (p < 0.05). Despite these changes, no statistically significant differences were found in terms of CSC colony number at different temperatures regardless of the presence or absence of HCQ. Based on the data, the combination of photothermal therapy with HCQ at 49 degrees C can significantly abort the CSC clonogenic capacity compared to the control-matched group without HCQ (p < 0.0001). PCR array showed photothermal modulation of CSCs led to alteration of autophagy-related genes and promotion of co-regulator of apoptosis and autophagy signaling pathways. Factors related to autophagic vacuole formation and intracellular transport were significantly induced at a temperature of 49 degrees C (p < 0.05). We also note the expression of common genes belonging to autophagy and apoptosis signaling pathways at higher temperatures. Data showed tumoricidal effects of laser-irradiated GNRs by the alteration of autophagic response and apoptosis.

Açıklama

Anahtar Kelimeler

Graphene, Metastasis, Resistance, Apoptosis, Therapy, Death, Mice

Kaynak

Scientific Reports

WoS Q Değeri

Q2

Scopus Q Değeri

Q1

Cilt

12

Sayı

1

Künye