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  • br Fig a and b

    2022-05-04


    Fig. 6. a) and b) Photographs of supernatant and hemolysis percentage of RBC when rabbit blood is immersed with water, saline, CoNWs, CoNWs-GO, and CoNWs-GO-PEG. c) Cell viabi-lity of 3T3 and 4T1 LY3009120 after incubation with CoNWs, CoNWs-GO, and CoNWs-GO-PEG at a concentration of 50 μg/mL for 9 h. d) Cell via-bility of 3T3 and 4T1 cells with various con-centrations of CoNWs-GO-PEG for 9 h. Statistical significance: * p < 0.05.
    the critical concentration of CoNWs-GO-PEG that causes the death of 50% cells is about 87.5 μg/mL, which is estimated from Fig. 6d. Herein, 50 μg/mL is selected as the optimized concentration of CoNWs-GO-PEG to be investigated in the tumor elimination in vitro.
    3.8. Chemo/photothermal therapy in vitro
    To assess the chemotherapy efficacy of CoNWs-GO-PEG-DOX of different concentrations, CCK-8 assay was applied to evaluate the via-bility of 4T1 cells (Fig. S4b). 4T1 cells were preincubated with CoNWs-GO-PEG-DOX of concentrations ranging from 0 μg/mL to 50 μg/mL for 9 h. The result shows that the cell viability of 4T1 decreases gradually as the concentration of CoNWs-GO-PEG-DOX increases. A similar phe-nomenon can also be observed from the live/dead staining fluorescent images (Fig. S4a). To further investigate the efficacy of chemo-photo-thermal combined therapy in vitro, 4T1 cells incubated with CoNWs-GO-PEG-DOX (50 μg/mL) were irradiated by 808 nm laser for 10 min (1.9 W/cm2) after incubation for 1 h, and the cell viability was assessed after incubation for 9 h (Fig. 7b). More cells are killed after irradiation for 10 min (45%) compared with the group without laser (52%), in-dicating the effective motivation of DOX releasing and hyperthermal therapy via laser irradiation. It is also worth mentioning that CoNWs-GO-PEG group with laser leads to more cell death (69%) than the same group without irradiation (83%), further demonstrating the effective-ness of hyperthermal therapy. However, the control group displays negligible influence after irradiation for 10 min, consistent with the result of the live/dead staining fluorescent pictures in Fig. 7a.
    In PTT, a NIR laser is used to illuminate the target tumor, and the light energy is converted into heat through optical absorption, which is highly dependent on the photothermal transducer [63]. In our study, we use cobalt as the photothermal transducer, which not only absorbs at NIR frequencies but also is magnetic, which suggests it can be lo-calized under a magnetic field, preventing it from seeping out of the target tissue and damaging the surrounding tissue. Photothermal da-mage of tumor cells typically commences when tumor temperature reaches 41℃ [64], and the temperature of CoNWs-GO-PEG can reach 46℃ when exposed to an 808 nm laser irradiation at 1.5 W/cm2 in the 
    photothermal circle test, which proves that CoNWs-GO-PEG is sufficient for the photothermal therapy. Although CoNWs-GO-PEG can activate the photothermal effect and confine the damage to areas of interest with minimal collateral effects, it is not likely that PTT alone can be used to eradicate malignant cells because of the locally heterogeneous distribution of heat in the tumor [65]. Therefore, it would be optimal to integrate PTT with other strategies such as chemotherapy. Herein, we combine CoNWs-GO-PEG and DOX that can be released at the tumor site, which is induced by the reduction of pH and the increase of tem-perature caused by the photothermal effect. Therefore, we conclude that CoNWs-GO-PEG-DOX presents the synergistic effect of tumor chemo-photothermal therapy in vitro. r> 4. Conclusions
    In summary, we present a new kind of CoNWs based multifunctional nanocarriers, which is structurally composed of cobalt nanowires de-corated with GO and PEG. The decoration of GO and PEG reduced the cytotoxicity of pure CoNWs obviously, and the nanosystem shows fa-vorable biocompatibility and excellent photothermal capacity that can be used as a therapeutic agent capable of targeting in the elimination of cancer cells. Furthermore, this nanocarrier possesses high DOX loading capacity (at least 992.91 mg/g), and the drug release behavior is meanwhile responsive to pH/NIR stimulation. Based on the excellent properties CoNWs-GO-PEG owns, CoNWs-GO-PEG-DOX shows a sa-tisfactory effect of eliminating cancer cells with chemo-photothermal synergistic therapy in vitro. Moreover, the photoacoustic imaging property of cobalt-based nanostructure is also of great significance in the localizing of nanocarriers in the tumor area, which may be mean-ingful in the diagnosis and therapeutic evaluation and thus worth fur-ther investigating. The present results suggest the exciting potential for CoNWs-GO-PEG nanocarriers serving as a practical and effective anti-tumor agent with a targeting capacity which can combine che-motherapy and photothermal therapy in cancer therapy.