Wenbin Lin

The efficacy of photodynamic therapy (PDT) depends on the subcellular localization of photosensitizers. Herein, we report a dual‐organelle‐targeted nanoparticle platform for enhanced PDT of cancer. By grafting 5‐aminolevulinic acid (ALA) to a Hf12‐based nanoscale metal‐organic layer (Hf‐MOL) via carboxylate coordination, ALA/Hf‐MOL enhanced ALA delivery and protoporphyrin IX (PpIX) synthesis in mitochondria, and trapped the Hf‐MOL comprising 5,15‐di‐p‐benzoatoporphyrin (DBP) photosensitizers in lysosomes. Light irradiation at 630 nm simultaneously excited PpIX and DBP to generate singlet oxygen and rapidly damage both mitochondria and lysosomes, leading to synergistic enhancement of the PDT efficacy. The dual‐organelle‐targeted ALA/Hf‐MOL outperformed Hf‐MOL in preclinical PDT studies, with a 2.7‐fold lower half maximal inhibitory concentration in cytotoxicity assays in vitro and a 3 …

Metal–organic layers (MOLs), a monolayered version of metal–organic frameworks (MOFs), have recently emerged as a novel two-dimensional molecular material platform to design multifunctional catalysts. MOLs inherit the intrinsic molecular tunability of MOFs and yet have more accessible and modifiable building blocks. Here we report molecular engineering of six MOLs via modulated solvothermal synthesis between HfCl4 and three photosensitizing ligands followed by postsynthetic modification with two carboxylate-containing cobaloximes for tandem and synergistic photocatalysis. Morphological and structural characterization by transmission electron microscopy and atomic force microscopy and compositional analysis by inductively coupled plasma-mass spectrometry and nuclear magnetic resonance spectroscopy establish the MOLs as flat nanoplates with a periodic lattice structure of hexagonal symmetry …

Despite significant efforts, it remains a challenge to design artificial enzymes that can mimic both structures and functions of natural enzymes. Here, we report the post-synthetic construction of binuclear iron catalysts in MOF-253 to mimic natural di-iron monooxygenases. The adjacent bipyridyl (bpy) linkers in MOF-253 can freely rotate to form the [(bpy)FeIII(μ2-OH)]2 active site in a self-adaptive fashion. The composition and structure of the [(bpy)FeIII(μ2-OH)]2 active sites in MOF-253 were characterized by a combination of inductively coupled plasma–mass spectrometry, thermogravimetric analysis, X-ray absorption spectrometry, and Fourier-transform infrared spectroscopy. The MOF-based artificial monooxygenase effectively catalyzed oxidative transformations of organic compounds, including C–H oxidation and alkene epoxidation reactions, using O2 as the only oxidant, which indicates the successful …

The combination chemotherapy regimen FOLFIRINOX comprising folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin is the first-line treatment for patients with advanced pancreatic cancer, but its use remains prohibitive for the majority of patients due to severe side effects. Here, we report a core-shell nanoscale coordination polymer (NCP) nanoparticle co-delivering a potent and synergistic combination of oxaliplatin, gemcitabine, and SN38 (OGS), for the treatment of pancreatic cancer in mouse models. OGS contains key synergistic components of FOLFIRINOX in a controllable drug ratio., It exhibited particle stability in blood circulation and enhanced deposition of the drugs in acidic tumor environments. In vitro, OGS showed superior cytotoxicity over free drug combinations and robust cytotoxic synergism among its three components. In vivo, OGS improved drug circulation, increased tumor deposition, and …

We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle …

The addition of immune checkpoint blockade to standard chemotherapy has changed the standards of care for some cancer patients. However, current chemo‐immunotherapy strategies do not benefit most colorectal cancer patients and many triple‐negative breast cancer patients. Here, the design of a three‐in‐one nanoscale coordination polymer (NCP), OX/GC/CQ, comprising prodrugs of oxaliplatin (OX), gemcitabine (GC), and 5‐carboxy‐8‐hydroxyquinoline (CQ) for triple‐modality chemo‐immunotherapy is reported. OX/GC/CQ exhibits optimal pharmacokinetics and enhanced particle accumulation and drug release in acidic tumor tissues, wherein CQ greatly enhances immunogenic cell death induced by OX/GC and downregulates programmed cell death‐ligand 1  expression in cancer cells. Consequently, OX/GC/CQ efficiently promotes infiltration and activity of cytotoxic T lymphocytes, while decreasing the …

Conventional chemotherapy targets proliferative cancer cells to halt tumor progression or regress tumors. However, the plasticity of tumor cells enables their phenotypical changes to acquire chemo-resistance, leading to treatment failure or tumor recurrence after a successful treatment course. Here, we report the use of high-dose pharmacologic ascorbate to potentiate treatment efficacy of nanoscale coordination polymers (NCPs) delivering two clinical combinations of chemotherapeutics, carboplatin/docetaxel and oxaliplatin/SN38, and to target metabolic plasticity of tumor cells. Combination treatments of high-dose ascorbate and NCPs overcome multi-drug resistance by significantly reducing the abundance of cancer stem cells (CSCs) in solid tumors, as evidenced by reduced expression of tumor pluripotency factors. The clearance of CSCs inhibits post-surgery recurrence and systemic metastasis in multiple …

Although many monometallic active sites have been installed in metal–organic frameworks (MOFs) for catalytic reactions, there are no effective strategies to generate bimetallic catalysts in MOFs. Here we report the synthesis of a robust, efficient, and reusable MOF catalyst, MOF‐NiH, by adaptively generating and stabilizing dinickel active sites using the bipyridine groups in MOF‐253 with the formula of Al(OH)(2,2′‐bipyridine‐5,5′‐dicarboxylate) for Z‐selective semihydrogenation of alkynes and selective hydrogenation of C=C bonds in α,β‐unsaturated aldehydes and ketones. Spectroscopic studies established the dinickel complex (bpy⋅−)NiII(μ2‐H)2NiII(bpy⋅−) as the active catalyst. MOF‐NiH efficiently catalyzed selective hydrogenation reactions with turnover numbers of up to 192 and could be used in five cycles of hydrogenation reactions without catalyst leaching or significant decrease of catalytic activities …