Smart Approach for In Situ One‐Step Encapsulation and Controlled Delivery of a Chemotherapeutic Drug using Metal–Organic Framework–Drug Composites in Aqueous Media

Abstract

Controlled release of an anticancer drug, doxorubicin (dox), from metal-organic framework (MOF)-drug composites is demonstrated under different external stimuli. 1,3,5-Benzenetricarboxylic acid (H3 BTC) is used as an organic ligand, and iron acetate and zinc nitrate are used as metal sources to synthesize Fe-BTC and Zn-BTC MOFs, which are known to be biocompatible. The in situ formation of MOF-drug composites demonstrates high drug loading capacity compared to conventional methods. The present methodology is devoid of any extra steps for loading the drug after synthesis. Moreover, the drug loading is also independent of pore size of the MOF as the drug molecules are embedded inside the MOF during their in situ formation. The drug release was monitored under external stimuli including change to acidic pH and the presence of biocompatible liposomes for a period of more than 72 h. Steady-state fluorescence spectroscopy is used to monitor the drug release as a function of time and confocal laser scanning microscopy is used to unravel the post-release fate of doxorubicin in the presence of liposomes. It is found that drug release rate is higher for the Zn-BTC-dox composite than for the Fe-BTC-dox composite. This is attributed to the stronger binding between dox and Fe-BTC than that between dox and Zn-BTC. This study highlights a novel approach for the preparation of MOF-drug composites in an aqueous medium for future biomedical applications.

Recent advances in metallopolymer-based drug delivery systems

“…A redox-and thermos-responsive gated supramolecular star polymers were obtained using the host-guest complexation of a 6-fold b-CD functionalized core molecule and Fc end modied poly(N,Ndimethylacrylamide) and poly(N,N-diethylacrylamide) linear polymers. 250 In addition to the similar systems discussed here, it should be noted the development of temperature-, [251][252][253] pressure-, 254 humidity-, 255 competitive binding agent-, 256,257 liposomeresponsive 258 and other stimuli-responsive metallopolymers used as DDSs. However, using multiple stimuli-responsive polymers is more effective to achieve more precise cancer therapies.…”

Metal–Organic Framework (MOF)‐Based Drug/Cargo Delivery and Cancer Therapy

“…Some other attempts have been made to design multiresponsive MOFs carriers in addition to the above‐mentioned supramolecular nanovalves systems. For instance, two biocompatible MOFs Fe‐BTC and Zn‐BTC (BTC = 1,3,5‐benzenetricarboxylic acid) have been investigated for one‐pot encapsulation of DOX at room temperature . Drug release could be triggered in the presence of biocompatible liposomes and lower pH, as carboxylate anions are protonated in acidic environments and break down the coordination between carboxylic acid group and metal center, leading to drug release by disruption of the MOF.…”

Metal–Organic Framework‐Based Stimuli‐Responsive Systems for Drug Delivery

“…Although rapid progress has been made on the study of stimuli-responsive MOF-based drug delivery systems, there are still many issues that should be addressed before their clinical application. [20] CPT/ZIF-8 [21] DOX/ZIFs [23] DOX/MSN@ZIF-8 [24] Fluorescein/ZIF-8@GO [25] DOX/Fe 3+ -catechol [26] 5-FU/UCNP@ZIF-8@FA [27] DOX/Fe 3 O 4 @C@ZIF-8 [28] DOX/IRMOF-3@FA [29] IBU/Zn-MOF [30] DOX/Fe-bbi@Silica@FA [31] DHA/Fe 3 O 4 @C@MIL-100(Fe) [33] ART/PB@MIL-100(Fe) [34] Glycoprotein/Fe-PBA [35] DOX/PPy@MIL-100(Fe) [36] DOX/Fe 3 O 4 @MIL-100(Fe) [37] AL/UiO-66(Zr) [38] DS/ZJU-101(Zr) [40] MTX/PCN-221(Zr) [41] Calcein/UiO-66(Zr) [42] DOX/Gd-PDBI [43] Antigens/Eu-MOF [44] TPPGC/Hf-BI [45] Rh6G (DOX)/CP5@Zn-MOF [80] 5-FU/CP5@Zr-MOF [85] DOX/Fe-BTC(Zn-BTC) [82] DOX/ZIFs [83] DOX/β-CD@MIL-100(Fe) [86] DOX/MIL-100(Fe) [87] DOX/P@ZIF-8 [89] MTX/Zn-TBDA [91] Rh6G/DNA@Zn-MOF [92] Magnetic NIM/Fe 3 O 4 @Cu 3 (BTC) 2 Magnetic-responsive materials [49] IBU/γ-Fe 2 O 3 @MIL-53(Al) [50] DOX/Fe-MOF [51] (MB+DOX)/Fe-MOF [52] Ions Procainamide HCl/BioMOF-1 Electrostatic interactions [53] IBU anions/MOF-74-Fe(III) [54] 5-FU/MOF-In1 [55] 5-FU/C...…”

“…In the presence of liposomes, drugs loaded in MOFs can be released due to electrostatic interactions between the drugs and liposomes. Adhikari et al prepared two DOX‐encapsulated biocompatible MOFs (Fe‐BTC and Zn‐BTC; BTC, 1,3,5‐benzenetricarboxylic acid) via a simple one‐step reaction at room temperature. Compared with conventional routes, this in situ formation of DOX‐loaded MOFs achieved high drug loading capacities (83% and 92% for Zn‐BTC and Fe‐BTC, respectively).…”