Combined and Single Doxorubicin/Naproxen Drug Loading and Dual-Responsive pH/Ultrasound Release from Flexible Metal-Organic Framework Nanocarriers

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In this study, the flexible aluminum-based MIL-53(Al) metal-organic framework was loaded with doxorubicin (DOX) and naproxen (NAP) and was examined as a promising pH/ultrasound dual-responsive drug delivery system. The two drugs were encapsulated in MIL-53(Al) individually to produce the DOX@MIL-53(Al) and NAP@MIL-53(Al) nanocarriers. They were also encapsulated as a dual-drug formulation to produce the DOX* + NAP*@MIL-53(Al) nanocarrier. The MOF nanoparticles were characterized using the Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), and Dynamic Light Scattering (DLS) techniques. In the case of the DOX@MIL, the nanocarriers’ drug Encapsulation Efficiency (EE) and Encapsulation Capacity (EC) were 92% and 16 wt.%, respectively, whereas, in the case of NAP@MIL-53(Al), the average NAP EE and EC were around 97.7% and 8.5 wt.%, respectively. On the other hand, in the DOX* + NAP*@MIL-53(Al) nanoparticles, the average DOX* EE and EC were 38.9% and 6.22 wt.%, respectively, while for NAP*, the average EE and EC were 70.2% and 4.49 wt.%, respectively. In vitro release experiments demonstrated the good pH and Ultrasound (US) dual-responsiveness of these nanocarriers, with a maximum US-triggered DOX and NAP release, at a pH level of 7.4, of approximately 53% and 95%, respectively. In comparison, the measured release was around 90% and 36% at pH 5.3 for DOX and NAP, respectively. In the case of the dualdrug formulation, the nanocarrier displayed similar pH/US dual-responsive behavior. Finally, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results confirmed the biocompatibility and low cytotoxicity of MIL-53(Al) at concentrations up to 1000 μg/ml.