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Metal-Organic Frameworks (MOFs) have emerged as a promising biomedical material due to its unique features such as high surface area, pore volume, variable pore size, flexible functional groups, and excellent efficiency for drug loading. In this review, we explored the use of novel and smart metal organic frameworks as drug delivery vehicles to discover a safer and more controlled mode of drug release aiming to minimize their side effects. Here, we systematically discussed the background of MOFs following a thorough review on structural and physical properties of MOFs, their synthesis techniques, and the important characteristics to establish a strong foundation for future research. Furthermore, the current status on the potential applications of MOF-based stimuli-responsive drug delivery systems, including pH-, ion-, temperature-, light-, and multiple responsive systems for the delivery of anticancer drugs has also been presented. Lastly, we discuss the prospects and challenges in implementation of MOF-based materials in the drug delivery. Therefore, this review will help researchers working in the relevant fields to enhance their understanding of MOFs for encapsulation of various drugs as well as their stimuli responsive mechanism., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pollution, unhygienic conditions and organic waste are detrimental to human health. On the contrary, animals living in polluted environments, feeding on organic waste and exposed to noxious agents such as heavy metals must possess remarkable properties against contracting diseases. Species such as cockroaches and water monitor lizards thrive in unhygienic conditions and feed on decaying matter. Here, we investigated the antitumour properties of metabolites produced by gut bacteria isolated from Varanus salvator (Asian water monitor lizard). An adult water monitor lizard and a juvenile water monitor lizard were acquired, and dissected. Their aerobic gut bacteria were isolated and identificated through 16S rDNA sequencing. Next, bacterial conditioned media (CM) were prepared and utilised for subsequent assays. Growth inhibition, MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay, cytotoxicity and cell survival assays were accomplished against a panel of cancer cells as well as a normal cell line. Furthermore, liquid chromatography-mass spectrometry (LC-MS) was employed to identify potential antitumour molecules. A plethora of bacteria were isolated from the gut of juvenile and adult V. salvator respectively. Moreover, CM prepared from selected bacteria exhibited antitumour activity. Of note, LC-MS results indicated the presence of several molecules with reported antitumour activity, namely, 3-butylidene-7-hydroxyphthalide, C75, enigmol, estrone 16-oxime, proglumide and S-allyl-L-cysteine. Furthermore, 356 potentially novel molecules from juvenile V. salvator and 184 from adult V. salvator were depicted. Thus, the gut microbiota of V. salvator might be considered as a great niche of antitumour molecules; however, further in vitro and in vivo studies are needed to assess the antitumour properties of these molecules.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Anti-neoplastic drugs used for cancer treatment often produce damage to healthy cells, leading to severe side effects in patients undergoing chemotherapy. The encapsulation of these agents in nanoparticles reduces the adverse side effects of conventional chemotherapy on healthy tissues. Such nanoparticles, considered as drug delivery vehicles, are diverse and include micelles, liposomes, dendrimers, nanocapsules, nanospheres and others. Polymeric micelles have been widely researched as nanocarriers for hydrophobic drugs. They can be designed to have increased stability and blood circulation time, as well as binding specificity to certain receptors overexpressed on the surface of cancer cells. Once these drug-encapsulating nanoparticles reach the tumor site, an external stimulus, such as ultrasound, can be used to spatially and temporally trigger drug release., Methods: This review paper focuses on the recent advances of cancer drug delivery systems employing polymeric micelles and ultrasound. An extensive literature review was performed mainly using PubMed. The introduction explains how nanocarriers are related to chemotherapy and the several modalities of use for this application. Afterwards, the review focuses on polymeric micelles used for drug delivery, their advantages and disadvantages. Subsequently, the physics of ultrasound is briefly reviewed, as well as the way it interacts with polymeric micelles to trigger the delivery of the drug transported by these nanocarriers. The following section focuses on targeting, discussing the several ways by which the nanoparticles can be directed to the target cells, and there deliver their cargo. Finally, a selection of relevant in vitro and in vivo studies, as well as clinical trials, is presented and discussed., Conclusion: Although there are still several research studies to be performed before the combination of micelles and ultrasound can enter clinical trials, the future of controlled delivery using this drug delivery system is promising as a way to reduce the mortality and morbidity of cancer and the noxious side effects of conventional chemotherapy.

Chemotherapy is widely used for cancer treatment; however, it causes unwanted side effects in patients. To avoid these adverse effects, nanocarriers have been developed, which can be loaded with the chemotherapeutic agents, directed to the cancer site and, once there, are exposed to stimuli that will trigger the drug release. Liposomes can be chemically modified to increase their circulation time, their stability, and their sensitivity to specific stimulus. Additionally, ligands can be conjugated to their surface, allowing for their specific binding to receptors overexpressed on the surface of cancer cells and the subsequent internalization via endocytosis. Using a triggering mechanism, including temperature, ultrasound, enzymes or a change in pH, the release of the drug is controlled and induced inside the cells, hence avoiding drug release in systemic circulation, which in turn reduces the undesired side effects of conventional chemotherapy. Ultrasound has been widely studied as a drug release trigger from liposomes, due to its well-known physics and previous uses in medicine. This review focuses on liposome-based drug delivery systems, using different trigger mechanisms, with a focus on ultrasound. The physical mechanisms of ultrasound release are also investigated and the results of in vitro and in vivo studies are summarized.