GNRs@SiO2-FA in combination with radiotherapy induces the apoptosis of HepG2 cells by modulating the expression of apoptosis-related proteins

Abstract

The aim of the present study was to examine the apoptosis of the hepatocellular carcinoma cell line, HepG2, induced by treatment with folic acid-conjugated silica-coated gold nanorods (GNRs@SiO2-FA) in combination with radiotherapy, and to determine the involvement of apoptosis-related proteins. An MTT colorimetric assay was used to assess the biocompatibility of GNRs@SiO2-FA. The distribution of GNRs@SiO2-FA into the cells was observed using transmission electron microscopy (TEM). HepG2 cells cultured in vitro were divided into the following 4 groups: i)the control group (untreated), ii) the GNRs@SiO2-FA group, iii) the radiotherapy group (iodine 125 seeds) and iv) the combination group (treated with GNRs@SiO2-FA and iodine 125 seeds) groups. The apoptosis of the HepG2 cells was detected by flow cytometry. The concentration range of <40 µg/ml GNRs@SiO2-FA was found to be safe for the biological activity of the HepG2 cells. GNRs@SiO2-FA entered the cytoplasm through endocytosis. The apoptotic rates of the HepG2 cells were higher in the GNRs@SiO2-FA and radiotherapy groups than in the control group (P<0.05). The apoptotic rate was also significantly higher in the combination group than the GNRs@SiO2-FA and radiotherapy groups (P<0.05). Taken together, these findings demonstrate that the combination of GNRs@SiO2-FA and radiotherapy more effectively induces the apoptosis of HepG2 cells. These apoptotic effects are achieved by increasing the protein expression of Bax and caspase-3, and inhibiting the protein expression of Bcl-2 and Ki-67. The combination of GNRs@SiO2-FA and radiotherapy may thus prove to be a new approach in the treatment of primary liver cancer.

Selective heat generation in cancer cells using a combination of 808 nm laser irradiation and the folate-conjugated Fe2O3@Au nanocomplex

“…The surface functionalization of Fe 2 O 3 @Au NPs with FA thus provides an active targeting strategy that directs the NPs towards the cell surface FA receptor, leading to enhanced uptake and efficient internalization of the NPs via receptor-mediated endocytosis [24,25]. For example, Gao et al [44] evaluated the targeting efficiency of FA-conjugated silica-coated gold nanorods (FA-SiO 2@ AuNR) towards the HepG2 hepatocellular carcinoma cells and reported a 2.65-fold higher cellular uptake rate for this noncomplex in comparison to the non-FA conjugated nanocomplex. In another study, the facility of FA targeting was utilized for improving the PTT efficiency of the KB cancer cells.…”

The benefits of folic acid-modified gold nanoparticles in CT-based molecular imaging: radiation dose reduction and image contrast enhancement

“…Zhou et al reported a targeted chemotherapy strategy for the efficient delivery of gold nanoclusters (AuNCs) carrying cisplatin prodrug and demonstrated an accelerated cellular internalization and enhanced tumour accumulation accompanied by the retention of the nanocarriers due to FA modification [36]. Remarkable successes in improving radiotherapy effectiveness have also been provided by utilizing FA-modified AuNPs [37]. Furthermore, in our previous works, we have demonstrated the positive impact of FA targeting on the increase in the photothermal therapy efficiency of AuNPs [38,39].…”

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

“…et al, 2017;Jiang et al, 2017). Consequently, GSH-responsive become one of most popular redox-responsive precision delivery strategies because of the higher GSH level in intracellular matrix of HCC cells than that in extracellular matrix or intracellular matrix of normal Chen et al, 2010Chen et al, , 2019Gao B. et al, 2015;Lv et al, 2015;Wang Y. et al, 2016;Wang et al, 2017a,b; RGD Integrin SMMC-7721, HepG2, Huh7…”

“…Usually normal cells possess a higher heat tolerance over cancer cells at elevated temperatures around 43 • C, so the heat generated (43 • C) would trigger the death of tumor cells only (El-Boubbou, 2018). Gao B. et al (2015), reported MSNs with gold core acted as a radiation sensitizer, thereby inducing the more effective radiotherapy by iodine 125 seed. Furthermore, Wang et al (2019) rethink that radiosensitization strategy is not sufficient because of the hypoxic microenvironment in HCC, so they fabricated Janus-structured gold triangle-mesoporous silica nanoparticles to ameliorates hypoxia through PTT generated by gold triangle.…”