Metal-Organic Framework/Graphene Quantum Dot Nanoparticles Used for Synergistic Chemo- and Photothermal Therapy

Abstract

In this study, a simple one-pot method was used to prepare a multifunctional platform for synergistic chemo- and photothermal therapy,, which is composed of zeolitic imidazolate framework-8 (ZIF-8) as drug nanocarriers and the embedded graphene quantum dots (GQDs) as local photothermal seeds. The structure, drug release behavior, photothermal effect, and synergistic therapeutic efficiency of the ZIF-8/GQD nanoparticles were systematically investigated. Using doxorubicin (DOX) as a model anticancer drug, the results showed that monodisperse ZIF-8/GQD nanoparticles with a particle size of 50-100 nm could encapsulate DOX during the synthesis procedure and trigger DOX release under acidic conditions. The DOX-loaded ZIF-8/GQD nanoparticles could efficiently convert near-infrared (NIR) irradiation into heat and thereby increase the temperature. More importantly, with breast cancer 4T1 cells as a model cellular system, the results indicated that the combined chemo- and photothermal therapy with DOX-ZIF-8/GQD nanoparticles exhibited a significant synergistic effect, resulting in a higher efficacy to kill cancer cells compared with chemotherapy and photothermal therapy alone. Hence, ZIF-8/GQD nanoparticles would be promising as versatile nanocarriers for synergistic cancer therapy.

Figure 1

Schematic illustration of the synthesis of ZIF-8/GQD nanoparticles with encapsulation of DOX molecules and synergistic DOX delivery and photothermal therapy.

Figure 2

SEM and TEM images of ZIF-8 (A,D), ZIF-8/GQD (B,E), and DOX-ZIF-8/GQD (C,F) nanoparticles.

Figure 3

Wide-angle XRD patterns of GQDs, DOX, ZIF-8, ZIF-8/GQD, ZIF-8-GQDs-M, and DOX-ZIF-8/GQD nanoparticles.

Figure 4

FTIR spectra of GQDs, DOX, ZIF-8, ZIF-8/GQD, ZIF-8-GQDs-M, and DOX-ZIF-8/GQD nanoparticles.

Figure 5

UV–vis spectra of the DOX solution and GQDs, ZIF-8, ZIF-8/GQD, and DOX-ZIF-8/GQD suspensions.

Figure 6

TG analysis of ZIF-8, ZIF-8/GQD, and DOX-ZIF-8/GQD nanoparticles.

Figure 7

Cumulative DOX release profiles of DOX-ZIF-8/GQD nanoparticles in the PBS buffer with pH 4.5, 6.0, and 7.4, separately.

Figure 8

SEM images of DOX-ZIF-8/GQD nanoparticles after immersing in PBS with pH 4.5, 6.0, and 7.4 for 4 and 8 h.

Figure 9

(A) Photothermal effects of DOX-ZIF-8/GQD nanoparticles using NIR irradiation (λ = 808 nm) at various laser intensities for 10 min; (B) Photothermal effects of DOX-ZIF-8/GQD nanoparticles in water and DMEM with different concentrations using 808 nm laser irradiation at 1.5 W/cm².

Figure 10

Cell viability of 4T1 cells after incubation with ZIF-8/GQD nanoparticles at different concentrations as measured using a CCK-8 assay.

Figure 11

Confocal microscope images of 4T1 cells after 4 h of incubation with (a) free DOX, (b) ZIF-8/GQD nanoparticles, and (c) DOX-ZIF-8/GQD nanoparticles (DOX: 0.5 μg/mL, ZIF-8/GQDs: 10 μg/mL): (A) 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) and DOX channels and (B) Differential interference contrast (DIC) and GQD channels.

Figure 12

(A) Bright-field images of 4T1 cells after 8 h of incubation (a) without free DOX solution and (b) with free DOX solution, (c) with ZIF-8/GQD, and (d) with DOX-ZIF-8/GQD suspensions (DOX: 5 μg/mL, ZIF-8/GQDs: 100 μg/mL), the images of a1–d1 were recorded without NIR irradiation, and the images of a2–d2 were recorded after NIR irradiation for 3 min. (B) Cell viability of 4T1 cells after 8 h of incubation without and with free DOX solution, ZIF-8/GQD, and DOX-ZIF-8/GQD suspensions (DOX: 5 μg/mL, ZIF-8/GQDs: 100 μg/mL) and without and with 3 min NIR irradiation.