Photothermal/pH Responsive B-CuS-DOX Nanodrug for Chemo-photothermal Synergistic Therapy of Tumor

doi:10.15541/jim20200394

Abstract

Abstract:

Nanoparticles-based drug delivery system for synergetic chemo-photothermal therapy is an efficient strategy for tumor therapy. However, construction of nanodrugs with high drug loading capacity and good photothermal conversion property is still a great challenge. In this work, two-dimensional boron nanosheets were prepared by ultrasonic liquid exfoliation method, which were further loaded with ultra-small copper sulfide (CuS) nanoparticles and doxorubicin (DOX) to obtain B-CuS-DOX nanocomposites. The prepared B-CuS-DOX exhibited high drug loading capacity (864 mg/g) and excellent photothermal conversion efficiency (55.8%). In addition, B-CuS-DOX exhibited pH and laser--responsive drug release behavior. In vitro results demonstrated that the prepared B-CuS-DOX achieved a good synergistic effect of chemotherapy and photothermal therapy. This work is expected to provide an effective chemo-photothermal synergistic therapy strategy for tumor therapy.

Key words: boron nanosheet, drug delivery, photothermal therapy, stimulus-responsive, tumor, synergistic therapy

CLC Number:

TQ174

XIE Xue, WU Jianrong, CAI Xiaojun, HAO Junnian, ZHENG Yuanyi. Photothermal/pH Responsive B-CuS-DOX Nanodrug for Chemo-photothermal Synergistic Therapy of Tumor[J]. Journal of Inorganic Materials, 2021, 36(1): 81-87.

Figures/Tables 7

Fig. 1 Characterization of B nanosheets, B-CuS and B-CuS-DOX TEM images of (A) B-CuS and (B) B-CuS; (C) Diameter of B-CuS-DOX; (D) XPS survey spectra of B nanosheets; (E) The selective XPS survey spectra corresponding to B1s spectra; (F) Hydrodynamic size change of B-CuS-DOX dispersed in saline, medium containing fetal bovine serum (FBS), human simulated body fluid (SBF) for 15 d; (G) UV-Vis-NIR spectra and (H) Zeta potential of B nanosheets, B-CuS and B-CuS-DOX; (I) Histogram of the relationship between DOX drug loading and DOX concentration. DOX: doxorubicin

Fig. 2 Photothermal performance of B-CuS (A) The temperature change of B-CuS dispersion with different concentrations within 5 min of laser irradiation with a power density of 0.5 W/cm2; (B) The temperature change of B-CuS (200 μg/mL) dispersion under different laser power densities for 5 min; (C) Thermal images of B-CuS dispersions with different concentrations after irradiation within 5 min with a laser power density of 0.5 W/cm2; (D) B-CuS photothermal curve under five laser “on-off” cycles; (E) The linear regression equation of the negative natural logarithm of B-CuS heating and cooling time and temperature, θ=ΔT/ΔTmax

Fig. 3 Drug release curves of B-CuS-DOX in PBS solution with different pH and with or without NIR laser irradiation

Fig. 4 In vitro cellular uptake of B-CuS-DOX (A) CLSM images of 4T1 cells treated with free DOX and B-CuS-DOX with or without laser irradiation; (B) Quantitative analysis of fluorescence intensity of DOX uptake by 4T1 cells in each treatment. Scale bar: 15 μm; *: p < 0.05. DOX: doxorubicin

Fig. 5 Evaluation of B-CuS-DOX on cell chemotherapy-PTT synergistic therapy (DOX: doxorubicin) (A) Cell survival rate of 4T1 cells incubated with different concentrations of B-CuS for 24 and 48 h; (B) Cell survival rate of 4T1 cells treated with different experimental groups; (C) Therapeutic efficacy of PTT, chemotherapy, chemo-photothermal synergistic therapy and additive therapy. *: p<0.05

Fig. 6 Observation of 4T1 cells stained with calcein AM and PI under confocal microscope (scale: 50 μm). DOX: doxorubicin

Fig. 7 Detection of apoptosis of 4T1 cells after different treatments by flow cytometry (DOX: doxorubicin)

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