Metal–Organic Framework (MOF) Hybrid as a Tandem Catalyst for Enhanced Therapy against Hypoxic Tumor Cells

Abstract

Encapsulation of active biomolecules and/or nanoparticles in metal-organic frameworks (MOFs) remains ag reat challenge in biomedical applications.I nt his work, through astepwise in situ growth method, ablack phosphorus quantum dot (BQ) and catalase were precisely encapsulated into the inner and outer layers of MOFs,r espectively.T he integrated MOF system as at andem catalyst could convert H 2 O 2 into O 2 in MOF-stabilized catalase outer layer,and then O 2 was directly injected into MOF-sensitized BQ inner,leading to high quantum yield of singlet oxygen. Upon internalization, the photodynamic therapye fficiency of the MOF system was 8.7-fold greater than that without catalase,s howing an enhanced therapeutic effect against hypoxic tumor cells. Furthermore,b yc oupling with photothermal therapyo fB Qs, photodynamic-thermal synergistic therapyw as realized both in vitro and in vivo. Functionalization of metal-organic frameworks (MOFs)with nanoparticles (NPs) or biomolecules has attracted great attention in catalysis,s eparation, and biomedical applications. [1] Fabrication of nanoparticle-functionalized MOFs (NP/MOFs) was usually divided into three different strategies:o ne-pot method to induce the NPs within the cavities of the MOF, [2] post-absorption of NPs onto the MOF surfaces [3] and in situ growth of MOF on pre-synthesized NPs. [4] TheN P/MOFs demonstrated efficient charge separation and excellent catalytic activity due to the uniform distribution of NPs and sensitization of MOFs. [5] On the other hand, the decoration of biomolecules,such as enzymes, DNA, and peptides,i nto MOFs was rare due to the lack of mild synthetic conditions. [6] Initially,e nzymes such as horseradish peroxidase were assembled on MOFs by surface attachment. [7] Later, ai nsitu encapsulated strategy was evolved to embed catalase into zeolitic imidazolate framework (ZIF) matrix via awater-based mild approach. [8] In our previous work, ap eptide-AuNP/ZIF-8 core-shell nanocomposite with high activity was established in am ild condition for imaging intracellular enzymes. [9] To date,the simultaneous distribution of nanoparticles and enzymes in aMOF structure remains ag reat challenge,w hich inspires us to generate aprogrammable platform as atandem catalyst for biomedical applications.Black phosphorus (BP) is ap romising metal-free nanomaterial in biological fields due to its instinct structure and good biocompatibility. [10] In particular,BPquantum dot (BQ) displays optical properties,s uch as both singlet oxygen ( 1 O 2 ) production and photothermal conversion efficiency for photodynamic therapy (PDT) and photothermal therapy (PTT), [11] respectively,o wing to the quantum confinement and edge effects. [12] Herein, for enhanced therapy in hypoxia, [13] aB Qa nd catalase co-encapsulated Materials of Institute Lavoisier (MIL-101)-type MOF heterostructure (BQ-MIL@cat-MIL) was constructed by the precise assembly of BQ in MIL to form the BQ-MIL inner,a nd followed by introduction of catalase into the outer layer of MIL (Scheme 1). Remarka...

Metal–Organic Frameworks for Biomedical Applications

“…d) Schematic illustration for the preparation of tandem catalytic MOF‐based platform and its application in enhancing the therapeutic effect of hypoxic tumor cells by PDT and PTT. Reproduced with permission 37. Copyright 2019, Wiley‐VCH.…”

“…36 In the as‐prepared Pda‐Pt@PCN‐FA nanofactory, the Pt nanoparticles (NPs) on the surface of polydopamine (Pda) core were used to catalyze the conversion of endogenous H 2 O 2 to O 2 to alleviate hypoxia in the TME and increase effect of PDT, the PCN shell consisted of tetrakis(4‐carboxyphenyl)porphyrin (H 2 TCPP) and Zr 4+ and attached with FA via coordination between Zr 6 and carboxyl groups of FA was used to reduce the interference between reactions, for converting O 2 into 1 O 2 , and shortening the diffusion distance of ROS. Recently, Lei and co‐workers reported a tandem catalytic MOF‐based platform combining PTT and PDT to enlarge the therapeutic effect of hypoxic tumor cells 37. BQ‐MIL@cat‐MIL heterostructure was built from a layered MIL‐101‐NH 2 that encapsulated black phosphorus quantum dot (BQ) as inner and catalase (CAT) as outer, respectively.…”

“…Recently, Lei and co-workers reported a tandem catalytic MOF-based platform combining PTT and PDT to enlarge the therapeutic effect of hypoxic tumor cells. [37] BQ-MIL@cat-MIL heterostructure was built from a layered MIL-101-NH 2 that encapsulated black phosphorus quantum dot (BQ) as inner and catalase (CAT) as outer, respectively. Furthermore, the surface of BQ-MIL@cat-MIL was modified with PEG-FA and cyanine 3 (Cy3)-labeled caspase substrate peptide (Cy3-pep) to obtain BQ-MIL@cat-fMIL for the enhanced targeting capacity and visualization (Figure 4d).…”

Integration of Self‐Luminescence and Oxygen Self‐Supply: A Potential Photodynamic Therapy Strategy for Deep Tumor Treatment

“…These strategies can be classified into two kinds. One kind is using various catalysts to catalyze the decomposition of hydrogen peroxide (H 2 O 2 ) into water and oxygen, and another kind is employing different oxygen carriers such as perfluorocarbons (PFCs) and hemoglobin (Hb) to deliver oxygen . Nanocomposites employed in PDT can be designed flexibly and smartly as required .…”

Optimizing Energy Transfer in Nanostructures Enables In Vivo Cancer Lesion Tracking via Near‐Infrared Excited Hypoxia Imaging

“…HeLa cell lines were selected as a bioassay model to inspect the performance of BMU‐Ru nanosensors toward O 2 detection in vitro under physiological condition. [ 54,55 ] Before investigation, the cytotoxicity of BMU‐Ru nanosensors was analyzed by CCK‐8 assay on both the hypoxic and normoxia HeLa cell lines with the added amount of BMU‐Ru nanosensors from 15–400 µg mL −1 (Figure S16, Supporting Information). The cell viability of HeLa cell lines under the hypoxic environment remains above 80% even after incubation with 400 µg mL −1 BMU‐Ru nanosensors for 24 h, indicating the very low cytotoxicity of BMU‐Ru nanosensors.…”