Optimized Metal–Organic-Framework Nanospheres for Drug Delivery: Evaluation of Small-Molecule Encapsulation

Abstract

We have developed a general synthetic route to encapsulate small molecules in monodisperse zeolitic imid-azolate framework-8 (ZIF-8) nanospheres for drug delivery. Electron microscopy, powder X-ray diffraction, and elemental analysis show that the small-molecule-encapsulated ZIF-8 nanospheres are uniform 70 nm particles with single-crystalline structure. Several small molecules, including fluorescein and the anticancer drug camptothecin, were encapsulated inside of the ZIF-8 framework. Evaluation of fluorescein-encapsulated ZIF-8 nanospheres in the MCF-7 breast cancer cell line demonstrated cell internalization and minimal cytotoxicity. The 70 nm particle size facilitates cellular uptake, and the pH-responsive dissociation of the ZIF-8 framework likely results in endosomal release of the small-molecule cargo, thereby rendering the ZIF-8 scaffold an ideal drug delivery vehicle. To confirm this, we demonstrate that camptothecin encapsulated ZIF-8 particles show enhanced cell death, indicative of internalization and intracellular release of the drug. To demonstrate the versatility of this ZIF-8 system, iron oxide nanoparticles were also encapsulated into the ZIF-8 nanospheres, thereby endowing magnetic features to these nanospheres.

A feasible synthesis of Mn 3 (PO 4 ) 2 @BSA nanoflowers and its application as the support nanomaterial for Pt catalyst

“…Zeng and co-workers reported a CaHPO 4 -α-amylase hybrid nanobiocatalytic system based on allosteric effect; catalytic activity increase was attributed to the immobilization of a certain enzymes [16]. So far, these nanoflowers have been utilized in the fields of colorimetric platform [17], colorimetric sensor [18], diverse biological molecular recognition [19], molecular recognition [20], and drug delivery [11]. This is the first report on the design and synthesis of a Mn 3 (PO 4 ) 2 @BSA hybrid nanoflower made of both protein and manganese (II) phosphate by using the method of self-assembly.…”

Bio-Inspired Metal-Organic Frameworks in the Pharmaceutical World: A Brief Review

“…"Smart" drug delivery of anticancer drugs is being explored making use of pH-sensitive systems [65][66][67][68]. The interest in the use of a pH-responsive drug vehicle is due to the fact that they can reduce undesired drug release during transportation in blood circulation and improve the effective release of the drug in the tumour tissue or within tumour cells [105,106].…”

“…In this study, the evaluation of fluorescein-encapsulated ZIF-8 in the MCF-7 breast cancer line demonstrated cell internalization and a minimal cytotoxicity. Furthermore, the pH-responsive dissociation of the ZIF-8 framework likely results in endosomal release of the small-molecule cargo proved that ZIF-8 can be an ideal drug delivery vehicle [68].…”

“…ZIFs simultaneously have the following characteristics of MOFs and zeolites, combining the advantages of both: ultrahigh surface areas, unimodal micropores, high crystallinity, various functionalities and exceptional thermal and chemical stabilities, making them very promising for biomedical applications [63,64]. Several studies describe the successful incorporation of anticancer drugs into ZIF-8 with positive results for the controlled pH-sensitive drug release and fluorescence imaging [65][66][67][68][69]. Also caffeine was already encapsulated into ZIF-8 showing a controlled release [70,71].…”

Interaction between transition metals and phenylalanine: A combined experimental and computational study

“…These metals have been used for drug design and delivery [12][13][14][15][16][17], catalysis [18][19][20][21], solar cell applications [22][23][24], and biological imaging [25,26]. In biological systems, transition metals are involved with very specific structural and cellular functions.…”