Received Date:
16 October 2019 Available Online:
15 January 2020
Abstract:
With the development of nanotechnology and its penetration into the field of medicine, nanotechnology has opened a new way for the treatment of tumors. Building an effective nanocarrier system is significant for the treatment of tumors. Compared with the traditional drug therapy, the drug which uses the nanomaterial as the carrier can greatly improve the treatment effect of the medicine and the side effect caused by the medicine in the in-vivo circulation process is extremely reduced simultaneously. At the same time, due to the protective effect of the carrier, the stability of the drug can be improved obviously. In this paper, we report a composite nanomaterial Bi@ZIF-8@TPZ (BZT) which is the formation of Bi nanoparticles and tirapazamine (TPZ) embedded in ZIF-8, this novel nanomaterial combines chemotherapy with photothermal therapy in the second near-infrared region (NIR-Ⅱ), and achieves a good therapeutic effect. First, we prepared a Bi@ZIF-8 (BZ) nanoparticle by a simple one-step reduction method. The morphology and microstructure of the nanoparticle were analyzed by transmission electron microscopy (TEM) and X-ray diffraction (XRD). Next, the anticancer drug tirapazamine (TPZ) was efficiently loaded into the BZ nanomaterial by physical mixing. The UV absorption spectrum proved that it could be successfully loaded, and the loading efficiency (LE) was 30%. Furthermore, the embedded Bi nanoparticles make the composite nanomaterials have good photothermal properties in NIR-Ⅱ area, and the photothermal conversion efficiency is about 31.75%. Because ZIF-8 has a good pH response ability, the material can achieve controllable drug release under weak acid (pH=5.5) and light conditions. In vitro results show that BZ loaded with the chemotherapeutic drug TPZ can achieve a good therapeutic effect. The composite materials reported in this article realize the synergistic treatment of chemotherapy and NIR-Ⅱ photothermal treatment, which makes it highly clinically useful.
Figure 1.
(A) SEM image of BZT nanoparticles; (B) TEM image of BZT nanoparticles; (C) elemental mapping images of C, Zn, O and Bi; (D) absorbance spectra of TPZ, BZ and BZT; (E) EDX analysis of BZT; (F) powder XRD pattern for BZ; (G) particle size of BZT
Figure 2.
(A) The infrared thermal images of PBS, TPZ, BZ and BZT nanoparticles (containing 100 μg/mL BZ) irradiated for 1~3 min (1064 nm, 1 W/cm2); (B) temperature rise curve of BZT with different concentrations (50, 100, 200 μg/mL) irradiated by laser at 1 W/cm2 for 6.5 min at 1064 nm; (C) the photothermal response of a 200 μg/mL BZT nanoparticles aqueous solution was carried out by a NIR laser (1064 nm, 1 W/cm2), and then the laser was turned off and repeated three times; (D) the photothermal response of an aqueous solution containing 200 μg/mL BZT nanoparticles with a NIR laser (1064 nm, 1 W/cm2), and then the laser was shut off; (E) linear time data versus －ln θ obtained from the cooling period of figure D
Figure 3.
(A) In vitro cytotoxicity of BZ against different cells in the absence of light irradiation; (B) in vitro cytotoxicity of different nanoparticles against 4T1 cells in the absence of light irradiation (Dark); (C) in vitro cytotoxicity of different nanomaterials against 4T1 cells in the presence of light irradiation (1064 nm, 1 W/cm2, 5 min); (D) NIR-triggered (1 W/cm2) release of TPZ from BZT at pH 7.4 and 5.5; (E) temperature rise curve of each material under light condition
Figure 4.
Fluorescence images of 4T1 cells co-stained with FDA (live cells, green) and PI (dead cells, red) upon the addition of different nanomaterials with irradiation (1064 nm, 1 W/cm2, 3 min). Scale bar: 50 μm
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Figure 1
(A) SEM image of BZT nanoparticles; (B) TEM image of BZT nanoparticles; (C) elemental mapping images of C, Zn, O and Bi; (D) absorbance spectra of TPZ, BZ and BZT; (E) EDX analysis of BZT; (F) powder XRD pattern for BZ; (G) particle size of BZT
Figure 2
(A) The infrared thermal images of PBS, TPZ, BZ and BZT nanoparticles (containing 100 μg/mL BZ) irradiated for 1~3 min (1064 nm, 1 W/cm2); (B) temperature rise curve of BZT with different concentrations (50, 100, 200 μg/mL) irradiated by laser at 1 W/cm2 for 6.5 min at 1064 nm; (C) the photothermal response of a 200 μg/mL BZT nanoparticles aqueous solution was carried out by a NIR laser (1064 nm, 1 W/cm2), and then the laser was turned off and repeated three times; (D) the photothermal response of an aqueous solution containing 200 μg/mL BZT nanoparticles with a NIR laser (1064 nm, 1 W/cm2), and then the laser was shut off; (E) linear time data versus －ln θ obtained from the cooling period of figure D
Figure 3
(A) In vitro cytotoxicity of BZ against different cells in the absence of light irradiation; (B) in vitro cytotoxicity of different nanoparticles against 4T1 cells in the absence of light irradiation (Dark); (C) in vitro cytotoxicity of different nanomaterials against 4T1 cells in the presence of light irradiation (1064 nm, 1 W/cm2, 5 min); (D) NIR-triggered (1 W/cm2) release of TPZ from BZT at pH 7.4 and 5.5; (E) temperature rise curve of each material under light condition
Figure 4
Fluorescence images of 4T1 cells co-stained with FDA (live cells, green) and PI (dead cells, red) upon the addition of different nanomaterials with irradiation (1064 nm, 1 W/cm2, 3 min). Scale bar: 50 μm
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