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  • Drug Storage and Delivery

    Introduction

    The undesired side effects and poor selectivity of chemotherapy drugs (such as doxorubicin (DOX) and carboplatin, and platinum-based drugs) during traditional tumor treatment process have prompted the emergence of drug delivery systems. The cornerstone of drug delivery is a vehicle that can degrade over a period of time, and release drugs in a sustained manner. Recently, various inorganic materials such as mesoporous silica nanoparticles, carbon structures, oxides and nitrides and organic materials including polymers, liposomes, and dendrimers have been used as carriers for drug delivery systems to improve the efficiency of therapeutic effects and reduce side effects. However, disadvantages like less drug loading capacity, lack of tunable porosity, and premature drug leakage have limited their application. While MOFs and COFs based on their salient properties, such as high surface area, adjustable pore shape, large pore volume, potential biocompatibility, biodegradability and modifiability have drawn significant investigation in the field of drug delivery.

    Drug Storage and DeliveryFig.1 (a) Generalized scheme for the use of MOFs and COFs as drug delivery
    vehicles. (b) In vivo conditions involved in the slow release of drugs.

    Requirements for Qualified Drug Delivery Carrier

    • Accurate controlled release and avoid the 'burst effect' to ensure the safety of drug delivery.
    • Be detectable by various imaging techniques to observe the release process.
    • Efficiently entrap drugs with high loading capacity.
    • Non-toxic and biocompatibility.

    Drug Delivery Using MOFs and COFs

    After years of rapid development of drug carrier design based on MOFs and COF, there are two stages for MOFs and COFs as a drug carrier, from normal carrier to stimuli-responsive carrier. So far, a series of molecules, such as Doxorubicin, 5-Fluorouracil (5-FU), and Quercetin, have been incorporated into MOFs and COFs for drug delivery.

    • Normal Carriers: Typical MOFs and COFs based drug delivery system are formed by encapsulating drug molecules in the nanocages of MOFs and COFs to achieve drug delivery and sustained release in the tumor microenvironment. For instance, Sun et al. introduced a pair of chiral non-interpenetrated nanoporous MOFs (1a-L, 1b-D,) named [(CH3)2NH2]2[Zn(TATAT)2/3]·3DMF·H2O (shown in Fig.2) for the delivery of anticancer drug 5-Fu. The as prepared MOF possesses a high loading capacity of 0.5 g/g and exhibits a sustained release of 5-Fu (1 week for complete release in phosphate buffered saline buffer, pH 7.4)[1]. Zhao and co-workers conducted cell experiments with two imine-linked 2D COF, PI-2-COF and PI-3-COF. Both two COFs showed high drug loading capacity for 5-FU, captopril and Ibuprofen and even reaching to 30 wt%. The release rates of 5-FU were similar for both PI-n-COFs and most drugs were released out within 3 days[2].

    Drug Storage and DeliveryFig.2 Side view of left-handed and right-handed double-stranded helical chains in 1a-L and 1b-D, respectively

    • Stimuli-Responsive Carriers: Stimuli-responsibility is one of most fascinating properties to achieve real-time monitoring and on-demand drug release. Smart MOFs and COFs with good responsiveness to various stimuli, such as pH, redox, light, magnetic field, temperature, ions, and ultrasound, have attracted tremendous attention to achieve on demand release in controlled drug delivery and cancer therapy. For instance, Zhang and co-workers reported a biocompatible multifunctional Fe-MIL-101 based drug delivery system with pH and glutathione (GSH) dual-responsiveness and good degradability for the delivery of anticancer drug doxorubicin[3] (the process of preparation of the drug delivery system and its application in tumor therapy are shown in Fig.3). Boronate and imine based COFs have the inherent acid sensitivity, beyond that, researchers have endowed these COFs with more environment responsive features to make the drug delivery and release in a controllable way. Lei and co-workers applied self-condensation of 4,40-phenylazobenzoyl diboronic acid to build single-layer photoresponsive COFs. Under UV irradiation, the COFs frameworks would be destroyed and release the gust, copper phthalocyanine. Moreover, the destruction of COFs could be recovered through annealing[4].

    Drug Storage and DeliveryFig.3 Schematic diagram for the preparation of the drug delivery system based on Fe-MIL-101 and its application in tumor therapy

    Interestingly, apart from carrying anti-cancer drugs, functional COFs can kill tumor cells by themselves.

    Advantages of Using MOFs and COFs in Drug Delivery

    • Multiple morphologies, different compositions, tunable sizes, and unique chemistry properties, making MOFs and COFs easier to accommodate a wide range of drug molecules with different properties.
    • High surface areas and large pore sizes enable high loading capacity.
    • Tunable pore structure for controlled release.
    • Weak coordination bonds ensure good biodegradability of MOFs, reversibility of the covalent linkages enables a better biodegradability of COFs.

    What Can Alfa Chemistry Do

    The MOFs and COFs produced by Alfa Chemistry have a promising future in the field of drug storage and delivery, which can effectively improve the treatment efficiency and reduce side effects in tumor therapy. Alfa Chemistry provides you with the most professional services and the most favorable prices to buy MOFs and COFs. If you have any problems, we will provide technical support for you. If you have special needs, we will develop a unique solution for you. Please don't hesitate to contact us.

    References:

    1. Sun C.Y.; et al. Chiral nanoporous metal-organic frameworks with high porosity as materials for drug delivery[J]. Advanced Materials, 2011, 23, 5629-5632.
    2. Bai L.; et al. Nanoscale covalent organic frameworks as smart carriers for drug delivery[J]. Chemical Communication, 2016, 52, 4128-4131.
    3. Wang X.J.; et al. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy[J]. Nanoscale, 2015, 7, 16061-16070.
    4. Liu C.; et al. A photoresponsive surface covalent organic framework: Surface-confined synthesis, isomerization and controlled guest capture and release. Chemistry (Easton), 2016, 22, 6768-6773.

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