Abstract
We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells.
Highlights
Radiotherapy is an indispensable treatment for patients with cancer
We found that PAMAM-coated silica nanoparticles (PCSNs) probes were internalized by targeted HER2-overexpressing breast cancer cells, which implies that better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while avoiding damage to normal cells
PCSN probes bound to the surface of SK-BR3 cells within 4 h and were internalized after incubation for 24 h in cell culture medium containing dispersed PCSN probes (PCSN concentration: 1200 ppm) (Figure 3)
Summary
Radiotherapy is an indispensable treatment for patients with cancer. Nearly half of cancer patients undergo radiotherapy to cure their disease [1,2]. Despite the benefits of radiotherapy in enhancing outcomes and reducing the mortality rate, many patients suffer from unfavorable side effects [2,3,4]. These side effects reduce the efficiency of radiotherapy due to incomplete planned dose distribution and result in lower baseline quality of life [2,3,4]. The use of radiosensitizers is one solution to maximize the efficiency of radiotherapy. Several drugs such as 5-fluorouracil (5-FU), cisplatin and gemcitabine have been used to enhance the effects of radiotherapy [5]. A new clinical molecular-targeted strategy—epidermal growth factor receptor (EGFR) combined with HER2 [5]—has been introduced, it is necessary to identify more effective radiosensitizers to increase the efficiency of radiotherapy and to reduce radiation damage to surrounding normal tissues
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