Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks, anti-cancer drug delivery systems have been developed recently using nanocarriers including liposomes, micelles, polyelectrolyte capsules and others. One of the recent class of nanoparticles investigated for chemotherapeutic use are metal organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or clusters and organic ligands. MOFs are used in many applications including gas/vapor separation, gas storage, catalysis, luminescent materials, and biomedical imaging. These structures have additional features that promote their use as drug carriers in the biomedical field. First, they are nontoxic, biodegradable and have the ability to carry high loadings of the anti-neoplastic agent due to their porous nature. Also, they have well-defined crystalline structures that can be characterized by different analytical techniques and their sizes are suitable to control their in vivo drug release. This paper reviews the methods used to synthesize MOFs and their recent use as antineoplastic drug delivery carriers.

Doxorubicin (DOX) is one of the most widely used anthracycline anticancer drugs due to its high efficacy and evident antitumoral activity on several cancer types. However, its effective utilization is hindered by the adverse side effects associated with its administration, the detriment to the patients’ quality of life, and general toxicity to healthy fast-dividing cells. Thus, delivering DOX to the tumor site encapsulated inside nanocarrier-based systems is an area of research that has garnered colossal interest in targeted medicine. Nanoparticles can be used as vehicles for the localized delivery and release of DOX, decreasing the effects on neighboring healthy cells and providing more control over the drug’s release and distribution. This review presents an overview of DOX-based nanocarrier delivery systems, covering loading methods, release rate, and the cytotoxicity of liposomal, micellar, and metal organic frameworks (MOFs) platforms.

Metal-organic frameworks (MOFs) are highly crystalline porous organic-inorganic materials that are comprised of metal salts and organic linkers. The common synthetic methodologies of MOFs include: solvothermal, microwave-assisted, electrochemical, mechanochemical, and sonochemical routes. The synthesized MOF particles can be characterized using several characterization techniques including: X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and other analytical techniques. Recently, MOFs have garnered increasing attention due to their potential applications in numerous areas including: catalysis, gas storage and separation, drug delivery, and others. In this research paper, a new metal-organic framework was synthesized successfully from iron nitrate and 2,6-naphthalenedicarboxylic acid (1) by means of microwave irradiation (Fe-NDC-M) and (2) solvothermally using a conventional electric oven (Fe-NDC-O). They were characterized using XRD, SEM, FTIR, energy-dispersive X-ray (EDS), thermogravimetric analysis (TGA), and N2 sorption experiments. The characterization results showed that the synthesized samples were crystals with a rod-like shape. The particle diameters ranged between 50-80 nm with a length of 300-450 nm. The BJH adsorption averagepore diameters were found to be 148.551 Å and 139.265 Å for Fe-NDC-M and Fe-NDC-O, respectively. As a result, the new Fe-NDC-MOF particles can be used as nanocarriers for anticancer drug delivery applications utilizing the enhanced permeability and retention effect.

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.