Incorporation of cisplatin into the metal–organic frameworks UiO66-NH₂ and UiO66 – encapsulation vs. conjugation

Abstract

This work demonstrates synthetic strategies for the incorporation of an anticancer drug, cisplatin, and a Pt(IV) cisplatin prodrug into two zirconium-based metal-organic-frameworks (MOFs): UiO66 and UiO66-NH 2 . Cisplatin was chosen due to its reported high potency in killing ca. 95% of different cancers. Two approaches for its incorporation were investigated: conjugation and encapsulation. In the conjugation route, a Pt(IV) cisplatin prodrug was incorporated into UiO66-NH 2 utilising its amine group in an amidecoupling reaction. In the second case, cisplatin was encapsulated into the large cavities of both MOFs.The presence of platinum was confirmed by energy-dispersive X-ray spectroscopy and microwave plasma-atomic emission spectroscopy. The cytotoxicity of the formulations was assessed on the A549 lung cancer cell line. The results show that the system in which cisplatin is conjugated to UiO66-NH 2 is more efficient in inducing cell death than the materials where cisplatin is encapsulated into the pores of the MOFs. This is consistent with the higher drug loading achieved with the conjugation technique. One disadvantage of cisplatin therapy is that it may lead to thrombosis and, as a consequence, to heart attack and cardiac arrest. To ameliorate this potential side effect, we investigated the incorporation of NO (which has been widely researched for its antithrombotic properties) into the drug-loaded MOFs. All the cisplatin or pro-drug loaded MOFs are able to entrap and then release NO. Furthermore, the amount of NO released from these formulations is much greater than from the pure MOFs. As a result, the drug delivery systems developed in this work have potentially potent double functionality.

Understanding the Incorporation and Release of Salicylic Acid in Metal‐Organic Frameworks for Topical Administration

“…The high SA loading (12.1 wt.%) corresponds to 1.54 mol of drug per mol of material. This value is in total agreement with the encapsulation rates obtained for pure UiO-66-NH 2 or its composites with other molecules (i. e., 4.9 wt.% cisplatin, [50] and 27 wt.% 5-fluorouracil in UiO-66-NH 2 ; [51] or 8.7 wt.% of SA in Fe 3 O 4 @SiO 2 @UiO-66-NH 2 ). [52] Notably, the incorporation of SA within the porosity of UiO-66-NH 2 was confirmed by the reduction of the N 2 sorption Table 1.…”

A Facile Method for Preparing UiO-66 Encapsulated Ru Catalyst and its Application in Plasma-Assisted CO2 Methanation

“…The FTIR spectra of Ru@UiO-66 and UiO-66 display the same peaks in the region of 4000 to 400 cm −1 . The broad absorption band in the region of 3700 to 3200 cm −1 corresponding to the stretching vibration of O-H, to a large extent, is attributed to the residual solvent and adsorbed water [1,40]. In addition, it can also be induced by the OH from deprotonation of the carboxylate groups.…”

Metal–organic frameworks vs. buffers: case study of UiO-66 stability

“…These buffers are often used as a medium for cell cultivation and molecular biochemistry, with MOFs having applications in drug delivery and as biosensors; TRIS buffers are also utilized as an environment for the post-synthetic modification of MOFs. [44][45][46] In all these cases, the buffer concentrations are between 0.01 and 1.0 M with a typical working pH of 7.5. Therefore, we concentrated on ascertaining the effects of a TRIS buffer having a pH 7.5 on the stability of UiO-66, by assessing the kinetics of terephthalate release from the UiO-66 framework in detail (Table 1).…”