Fe3O4@Au core-shell hybrid nanocomposite for MRI-guided magnetic targeted photo-chemotherapy.

The combination of multiple therapeutic and diagnostic functions is fast becoming a key feature in the area of clinical oncology. The advent of nanotechnology promises multifunctional nanoplatforms with the potential to deliver multiple therapeutics while providing diagnostic information simultaneously. In this study, novel iron oxide-gold core-shell hybrid nanocomposites (Fe3O4@Au HNCs) coated with alginate hydrogel carrying doxorubicin (DOX) were constructed for targeted photo-chemotherapy and magnetic resonance imaging (MRI). The magnetic core enables the HNCs to be detected through MRI and targeted towards the tumor using an external magnetic field, a method known as magnetic drug targeting (MDT). The Au shell could respond to light in the near-infrared (NIR) region, generating a localized heating for photothermal therapy (PTT) of the tumor. The cytotoxicity assay showed that the treatment of CT26 colon cancer cells with the DOX-loaded HNCs followed by laser irradiation induced a significantly higher cell death as opposed to PTT and chemotherapy alone. The in vivo MRI study proved MDT to be an effective strategy for targeting the HNCs to the tumor, thereby enhancing their intratumoral concentration. The antitumor study revealed that the HNCs can successfully combine chemotherapy and PTT, resulting in superior therapeutic outcome. Moreover, the use of MDT following the injection of HNCs caused a more extensive tumor shrinkage as compared to non-targeted group. Therefore, the as-prepared HNCs could be a promising nanoplatform for image-guided targeted combination therapy of cancer.

Insights into Nano-Photo-Thermal Therapy of Cancer: The Kinetics of Cell Death and Effect on Cell Cycle.

BACKGROUND: Despite considerable advances in nano-photo-thermal therapy (NPTT), there have been a few studies reporting in-depth kinetics of cell death triggered by such a new modality of cancer treatment. OBJECTIVE: In this study, we aimed to (1) investigate the cell death pathways regulating the apoptotic responses to NPTT; and (2) ascertain the effect of NPTT on cell cycle progression. METHODS: Folate conjugated gold nanoparticle (F-AuNP) was firstly synthesized, characterized and then assessed to determine its potentials in targeted NPTT. The experiments were conducted on KB nasopharyngeal cancer cells overexpressing folate receptors (FRs), as the model, and L929 normal fibroblast cells with a low level of FRs, as the control. Cytotoxicity was evaluated by MTT assay and the cell death mode (i.e., necrosis or apoptosis) was determined through AnnexinV/FITC-propidium iodide staining. Next, the gene expression profiles of some key apoptotic factors involved in the mitochondrial signaling pathway were investigated using RT-qPCR. Finally, cell cycle phase distribution was investigated at different time points post NPTT using flow cytometric analysis. RESULTS: The obtained results showed that KB cell death following targeted NPTT was greater than that observed for L929 cells. The majority of KB cell death following NPTT was related to apoptosis. RT-qPCR analysis indicated that the elevated expression of Bax along with the depressed expression of Bcl-xL, Survivin and XIAP may involve in the regulation of apoptosis in response to NPTT. Flow cytometric analysis manifested that 16-24 hours after NPTT, the major proportion of KB cells was in the most radiosensitive phases of the cell cycle (G2/M). CONCLUSION: This study extended the understanding of the signaling pathway involved in the apoptotic response to NPTT. Moreover, the potential effect of NPTT on sensitizing cancer cells to subsequent radiation therapy was highlighted.

Selective apoptosis induction in cancer cells using folate-conjugated gold nanoparticles and controlling the laser irradiation conditions.

In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells. Folate-conjugated gold nanoparticles (F-AuNPs) were synthesized by tailoring the surface of AuNPs with folic acid to enhance the specificity of NPTT. KB cancer cells, as a folate receptor over-expressing cell line, and L929 normal cells with low level of folate receptors were incubated with the synthesized F-AuNPs and then irradiated with various laser intensities and exposure durations. Following various regimes of NPTT, we assessed the level of cell viability and the ratio of apoptosis/necrosis. No significant cytotoxicity was observed for both cell lines at concentrations up to 40 µM of F-AuNPs. Moreover, no significant cell lethality occurred for various laser irradiation conditions. The viability of KB and L929 cells incubated with F-AuNPs (40 µM; 6 h) and then irradiated by laser (1 W/cm2; 2 min) was 57 and 83%, respectively. It was also demonstrated that the majority of cancer cell death is related to apoptosis (41% apoptosis of 43% overall cell death). In this process of F-AuNPs based NPTT, it may be concluded that the main factor determining whether a cell dies due to apoptosis or necrosis depends on laser irradiation conditions. In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells.

Photothermal therapy using folate conjugated gold nanoparticles enhances the effects of 6MV X-ray on mouth epidermal carcinoma cells.

The aim of this study was to develop an optimized method for preparation of folate conjugated gold nanoparticles (F-AuNPs) and to investigate its cytotoxic effects and cell apoptosis in combination with photothermal therapy (PTT) and radiotherapy (RT) for the treatment of mouth epidermal carcinoma cells KB. For this purpose, cells were treated with synthesized F-AuNPs at different concentrations for 6h and then irradiated them with laser beam (532nm, 0.5W/cm2, 15min). After photothermal therapy, the cells were exposed to 6MV X-ray with a single dose of 2Gy. MTT assay were performed to evaluate the cell survival rate and apoptosis was determined by flow cytometry using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. No significant cell damage or cell apoptosis from the individual treatment of laser light or F-AuNPs was observed, while viability of cells incubated with F-AuNPs and then exposed to the laser was significantly decreased. Additionally, our results demonstrated that F-AuNPs is good radiosensitizers even at a low concentration such as 20µM when megavoltage X-ray is used. Also, when KB cells were treated with F-AuNPs under both laser and X-ray irradiation, the cell viability substantially decreased more than F-AuNPs-enhanced PTT alone or F-AuNPs-enhanced RT alone. Flow cytometry assay clearly indicated that F-AuNPs-mediated photo-thermo-radio therapy significantly induced apoptosis. These results confirm that F-AuNPs is a promising and research-worthy nanoconjugate in the field of targeted photo-thermo-radiotherapy of cancer.