Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles

Abstract

Background Gold nanoparticles (GNPs) have been used to sensitize cancer cells and enhance the absorbed dose delivered to such cells. Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells. The aim of this study was to assess the possible radiosensitiazation effect of GNPs conjugated with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams. Materials and methods Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammospheres of MCF-7 cells. Atomic absorption spectroscopy confirmed the cellular uptake of the gold particles. Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay. Result AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells. Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio of 1.35 and 1.66 and 1.91 for MCf-7, MDA-MB-231 and mammosphere cells. Conclusion Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death. The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake. This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams. This is particularly important for future preclinical testing to open a new insight for the treatment of cancers.

Anticancer effect of locally applicable aptamer‐conjugated gemcitabine‐loaded atelocollagen patch in pancreatic cancer patient–derived xenograft models

“… 3 However, since its first introduction, 4 various studies reported the anticancer effect of AS1411 in various types of cancers. 5 , 6 , 7 , 8 We used a modified type of this aptamer (AS1411) demonstrated by C’C’T‐AS1411 (IO101) and C’C’T‐AS1411‐TGG (IO101L) (see Figure 2 ). We evaluated the effect of stability and solubility in C’C’T‐AS1411‐TGG (IO101L) compared with C’C’T‐AS1411 (IO101).…”

Current Status of Oligonucleotide-Based Protein Degraders

“…However, as evidenced previously, breast-cancer-cell-specific aptamer AS1411 can be conjugated with a PROTAC molecule (as inspired by antibody–drug conjugates) as a delivery means to selectively target cancer cells over normal cells [ 21 ]; this constitutes the third layer of precision targeting. One could use structurally modified AS1411 as an alternative [ 96 , 97 , 98 , 99 , 100 , 101 , 102 ], because AS1411 was withdrawn from clinical trials [ 103 ]. The main reason for the withdrawal of AS1411 from clinical trials was its insufficient anti-cancer activity; meanwhile, its safety issue was found to be good [ 44 ].…”

Matrices and Affinity Ligands for Antibody Purification and Corresponding Applications in Radiotherapy

“…For example, As1411 is a guanine-rich DNA aptamer with high specificity and affinity to nucleolin receptors which are only overexpressed on the plasma membrane of cancer cells. The specific interaction between As1411 and nucleolin has been used to mediate the highly specific targeting of radiosensitizers to cancer cells [ 126 , 127 , 128 , 129 ]. As1411-conjugated gold nanoparticles [ 128 ], gold nanoclusters [ 126 ], or silver nanoparticles [ 127 , 129 ] have been proved to be capable of acting as efficient radiosensitizers for cancer targeting treatment.…”