Hybrid liposome/metal-organic framework as a promising dual-responsive nanocarriers for anticancer drug delivery.

In this work, liposome-coated iron (III) benzene-1,3,5-tricarboxylate (Fe-BTC) metal-organic framework is examined as a promising pH/Ultrasound dual-responsive nanocarriers for doxorubicin (DOX) delivery. The successful coating of the MOF particles (Lip-Fe-BTC) with the phospholipid bilayer (PBL) was established by direct fusion into the synthesized liposomes. The liposome coating was verified using several techniques, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The DLS measurements showed an increase in the average particle diameter of liposomes from 150 nm to 163.1 nm for Lip-Fe-BTC particles. The Fe-BTC particles had the highest average particle diameter (287.3 nm). These results demonstrated that the PBL reduced the aggregation of the particles and improved their dispersity in the release medium. The TGA results demonstrated the MOF's excellent thermal stability. Furthermore, the nanocarrier's loading efficiency and capacity were determined to be ~90% and ~13.5 wt%, respectively. The in-vitro DOX release experiments demonstrated that the DOX-loaded Fe-BTC and liposome-coated Fe-BTC particles showed good pH and US dual-responsive capability, making them promising nanocarriers for drug delivery. The application of US enhanced DOX release from both Fe-BTC and liposome-coated Fe-BTC. In the case of Fe-BTC-DOX particles, the application of US enhanced the DOX release to around 38% and 67%, at pH levels of 7.4 and 5.3, respectively. Similarly, DOX release from the Lip-Fe-BTC-DOX particles reached ~35% and ~53%, at pH levels of 7.4 and 5.3, respectively. The MTT assay showed the biocompatibility and low cytotoxicity of these nanocarriers below 100 µg/ml.

Recent Advances in Metal-Organic Frameworks as Anticancer Drug Delivery Systems: A Review.

BACKGROUND: Metal-organic frameworks (MOFs), as attractive hybrid crystalline porous materials, are being increasingly investigated in biomedical applications owing to their exceptional properties, including high porosity, ultrahigh surface areas, tailorable composition and structure, and tunability and surface functionality. Of interest, in this review, is the design and development of MOF-based drug delivery systems (DDSs) that have excellent biocompatibility, good stability under physiological conditions, high drug loading capacity, and controlled/targeted drug release. OBJECTIVE: This review highlights the latest advances in MOFs as anticancer drug delivery systems (DDSs) along with insights on their design, fabrication, and performance under different stimuli that are either internal or external. The synthesis methods of MOFs, along with their advantages and disadvantages, are briefly discussed. The emergence of multifunctional MOF-based theranostic platforms is also discussed. Finally, the future challenges facing the developments of MOFs in the field of drug delivery are discussed. METHODS: The review was prepared by carrying out a comprehensive literature survey using relevant work published in various scientific databases. RESULTS: Novel MOFs in biomedical applications, especially in drug delivery, have shown great potential. MOF-based DDSs can be classified into normal (non-controllable) DDSs, stimuli-responsive DDSs, and theranostic platforms. The normal DDSs are pristine MOFs loaded with therapeutic agents and offer little to no control over drug release. Stimuli-responsive DDSs offer better spatiotemporal control over drug release by responding to either endogenous (pH, redox, ions, ATP) or exogenous stimuli (light, magnetism, US, pressure, temperature). The theranostic platforms combine stimuli-responsive drug delivery with diagnostic imaging functionality, paving the road for imaging-guided drug delivery. CONCLUSION: This review presented a summary of the various methods utilized in MOF's synthesis along with the advantages and disadvantages of each method. Furthermore, the review highlighted and discussed the latest developments in the field of MOF-based DDSs and theranostic platforms. The review is focused on the characteristics of MOF-based DDSs, the encapsulation of different anticancer drugs as well as their stimuli-responsive release.

Facile Ultrasound-Triggered Release of Calcein and Doxorubicin from Iron-Based Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are promising new nanocarriers with potential use in anticancer drug delivery. However, there is a scarcity of studies on the uptake and release of guest molecules associated with MOF nanovehicles, and their mechanism is poorly understood. In this work, newly developed iron-based MOFs, namely Fe-NDC nanorods, were investigated as potential nanocarriers for calcein (as a model drug/dye) and Doxorubicin (a chemotherapeutic drug (DOX)). Calcein was successfully loaded by equilibrating its solution with the MOFs nanoparticles under constant stirring. The calcein average encapsulation efficiency achieved was 43.13%, with a corresponding capacity of 17.74 wt.%. In-vitro calcein release was then carried out at 37°C in phosphate buffer saline (PBS) using ultrasound (US) as an external trigger. MOFs released an average of 17.8% (without US), whereas they released up to 95.2% of their contents when 40-kHz US at ~1 W/cm² was applied for 10 min. The Cytotoxic drug DOX was also encapsulated in Fe-NDC, and its In-vitro release profile was determined under the same conditions. DOX encapsulation efficiency and capacity were found to be 16.10% and 13.37 wt.%, respectively. In-vitro release experiments demonstrated significant release, reaching 80% in 245 minutes, under acoustic irradiation, compared to around 6% in the absence of US. Additionally, experimental results showed that Fe-NDC nanoparticles are biocompatible even at relatively high concentrations, with an MCF-7 IC50 of 1022 g/ml. Our work provides a promising platform for anticancer drug delivery by utilizing biocompatible Fe-NDC nanoparticles and US as an external trigger mechanism.