MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Abstract

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.

In Situ Synthesis of a Mesoporous MIL-100(Fe) Bacteria Exoskeleton

“…The possibility to form MIL-100­(Fe) using such conditions in aqueous media under a mild temperature (30 °C) was first assessed without any bacterium. After 21 h of reaction, a solid phase was recovered and characterized by Powder X-ray Diffraction (Figure ), showing a crystalline structure with Bragg peaks in agreement with the calculated pattern of MIL-100­(Fe) and with previous reports on MIL-100­(Fe) obtained under mild conditions. − To prepare the biohybrid, the same synthesis was conducted in the presence of P. putida ( ca 4 × 10 7 CFU mL –1 ). The PXRD pattern of the resulting biohybrid material was fully consistent with that of MIL-100­(Fe), indicating the successful in situ synthesis of MIL-100­(Fe) in the presence of the bacteria.…”

How Defects Impact the In Vitro Behavior of Iron Carboxylate MOF Nanoparticles

“…To decrease the adverse effects and improve the therapeutic capability, MTX has previously been delivered in several MOFs as a therapeutic agent, such as γCD-MOF, Cu-MOF, MOF-5­(Zn), and UiO-66-NH 2 (Zr), with drug loading ratio ranging from 3.6 to 78%. MTX has also been encapsulated in MIL-100 60°C . The cargo content reached 33.5%, and the release of the MTX was almost complete in 48 h in PBS, pH 7.4, at 37 °C.…”

“…MTX has also been encapsulated in MIL-100 60°C . 85 The cargo content reached 33.5%, and the release of the MTX was almost complete in 48 h in PBS, pH 7.4, at 37 °C. Sal has been delivered by nanoparticle systems for the advanced treatment of lung diseases 86,87 and detected by MOFs used as biosensors or immunosensors.…”

Recent advances in metal–organic frameworks for stimuli-responsive drug delivery

“…MTX and collagenase are encapsulated in different regions within the capsule, allowing the antioxidant effect of MTX and the degradation effect of collagenase to interact without interference. 204 Fe can undergo oxidation and reduction reactions in the body and is more sensitive to acidity, so it can be further used in drug delivery systems. The Fe-MOFs synthesized by Lin et al are pH-sensitive.…”