Maltotriose Conjugated Metal-Organic Frameworks for Selective Targeting and Photodynamic Therapy of Triple Negative Breast Cancer Cells and Tumor Associated Macrophages.
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ABSTRACT:
SUBMITTER: Sakamaki Y
PROVIDER: S-EPMC7567337 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo. Methods: By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity in vitro. For in vivo experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment. Results: The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the in vivo experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period. Conclusion: We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency.
| S-EPMC6134922 | biostudies-literature
Project description:BackgroundTriple-negative breast cancer (TNBC) is an aggressive, metastatic and apparently drug-resistant subtype of breast cancer with a higher immune response compared to other types of breast cancer. Photodynamic therapy (PDT) has been gaining popularity for its non-invasive nature, minimal side effects, and spatiotemporally controlled benifits. The use of metal-organic frameworks (MOFs) loaded with programmed death-ligand 1 inhibitors (iPD-L1) offers the possibility of combining PDT with immunotherapy.MethodHere, we construct PCN-224, a MOFs with good biocompatibility and biodegradability for the delivery of the PD-L1 small molecule inhibitor BMS-202 to achieve a synergistic anti-tumor strategy of PDT and immunotherapy. Hyaluronic acid (HA) modified PEG (HA-PEG) was synthesized for the outer layer modification of the nanocomplex, which prolongs its systemic circulation time.ResultsIn vitro cellular experiments show that the nanocomplexes irradiated by 660 nm laser has a strong ability to produce singlet oxygen, which effectively induce PDT. PDT with strong immunogenicity leads to tumor necrosis and apoptosis, and induces immunogenic cell death, which causes tumor cells to release danger associated molecular patterns. In combination with iPD-L1, the combination therapy stimulates dendritic cell maturation, promotes T-cell activation and intratumoral infiltration, and reshapes the tumor immune microenvironment to achieve tumor growth inhibition and anti-distant tumor progression.ConclusionsMOFs-based nano-systems as a platform for combination therapy offer a potentially effective strategy for the treatment of TNBC with high metastatic rates.
| S-EPMC10668380 | biostudies-literature
Project description:We use first-principles calculations to show that the square symmetry of two-dimensional (2D) metal-organic frameworks (MOFs) made from octaamino-substituted phthalocyanines and square planar Ni2+ ions, which enable strong conjugation of π electrons, has a critical impact on the magnetic properties of the lattice. In particular, we predict the unexpected emergence of a rare high-temperature ferromagnetic half-metallic ground state in one case. Among charge neutral MOFs made from (2,3,9,10,16,17,23,24)-octaiminophthalocyanine (OIPc) metallated with divalent first-row transition metal ions (M-OIPc; M = Cr2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+) and connected through square planar Ni-bisphenylenediimine moieties, NiMn-OIPc exhibits a half-metallic and ferromagnetic ground state with a large exchange energy resulting from the unique strong hybridization between the d/π orbitals of Mn, the Pc ring, and the Ni-bisphenylenediimine nodes. Notably, we show that for NiMn-OIPc there is a considerable difference between the ferromagnetic ordering temperature (Tc) predicted by a 2D Ising model, which exceeds 600 K, and a Tc of 170 K predicted by our more realistic Monte Carlo simulation that includes magnetic anisotropy. Critically, our simulations adopt two spin models that incorporate magnetic anisotropy in the form of exchange anisotropy and single-ion anisotropy. We further show that in the bulk, 2D layers of NiMn-OIPc adopt a slipped-parallel stacking configuration, and exhibit interlayer magnetic coupling that is sensitive to the relative in-plane displacement between adjacent layers. These results highlight the critical role of magnetic anisotropy in modeling the properties of 2D magnetic systems. More generally, it demonstrates that strong hybridization between open-shell ions and delocalized aromatic π systems with appropriate symmetry, combined with large magnetic anisotropy, will be an effective design strategy to realize ferromagnetic 2D MOFs with high Tc.
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Project description:The rise and spread of antimicrobial resistance is creating an ever greater challenge in wound management. Nanofibrous membranes (NFMs) incorporated with antibiotics have been widely used to remedy bacterial wound infections owing to their versatile features. However, misuse of antibiotics has resulted in drug resistance, and it remains a significant challenge to achieve both high antibacterial efficiency and without causing bacterial resistance. Here, the 'MOF-first' strategy was adopted, the porphyrinic metal-organic frameworks nanoparticles (PCN-224 NPs) were pre-synthesized first, and then the composite antibacterial PCN-224 NPs @ poly (ε-caprolactone) (PM) NFMs were fabricated via a facile co-electrospinning technology. This strategy allows large amounts of effective MOFs to be integrated into nanofibers to effectively eliminate bacteria without bacterial resistance and to realize a relatively fast production rate. Upon visible light (630 nm) irradiation for 30 min, the PM-25 NFMs have the best 1O2 generation performance, triggering remarkable photodynamic antibacterial effects against both S. aureus, MRSA, and E. coli bacteria with survival rates of 0.13%, 1.91%, and 2.06% respectively. Considering the photodynamic antibacterial performance of the composite nanofibrous membranes functionalized by porphyrinic MOFs, this simple approach may provide a feasible way to use MOF materials and biological materials to construct wound dressing with the versatility to serve as an antibacterial strategy in order to prevent bacterial resistance.
| S-EPMC8625335 | biostudies-literature
Project description:Bacterial biofilms are difficult to treat due to their resistance to traditional antibiotics. Although photodynamic therapy (PDT) has made significant progress in biomedical applications, most photosensitizers have poor water solubility and can thus aggregate in hydrophilic environments, leading to the quenching of photosensitizing activity in PDT. Herein, a benzoselenadiazole-containing ligand was designed and synthesized to construct the zirconium (IV)-based benzoselenadiazole-doped metal-organic framework (Se-MOF). Characterizations revealed that Se-MOF is a type of UiO-68 topological framework with regular crystallinity and high porosity. Compared to the MOF without benzoselenadiazole, Se-MOF exhibited a higher 1O2 generation efficacy and could effectively kill Staphylococcus aureus bacteria under visible-light irradiation. Importantly, in vitro biofilm experiments confirmed that Se-MOF could efficiently inhibit the formation of bacteria biofilms upon visible-light exposure. This study provides a promising strategy for developing MOF-based PDT agents, facilitating their transformation into clinical photodynamic antibacterial applications.
| S-EPMC9781904 | biostudies-literature
Project description:Photodynamic inhibition (PDI) of bacteria represents a powerful strategy for dealing with multidrug-resistant pathogens and infections, as it exhibits minimal development of antibiotic resistance. The PDI action stems from the generation of a triplet state in the photosensitizer (PS), which subsequently transfers energy or electrons to molecular oxygen, resulting in the formation of reactive oxygen species (ROS). These ROS are then able to damage cells, eventually causing bacterial eradication. Enhancing the efficacy of PDI includes the introduction of heavy atoms to augment triplet generation in the PS, as well as membrane intercalation to circumvent the problem of the short lifetime of ROS. However, the former approach can pose safety and environmental concerns, while achieving stable membrane partitioning remains challenging due to the complex outer envelope of bacteria. Here, we introduce a novel PS, consisting of a metal-free donor-acceptor thiophene-based conjugate molecule (BV-1). It presents several advantageous features for achieving effective PDI, namely: (i) it exhibits strong light absorption due to the conjugated donor-acceptor moieties; (ii) it exhibits spontaneous and stable membrane partitioning thanks to its amphiphilicity, accompanied by a strong fluorescence turn-on; (iii) it undergoes metal-free intersystem crossing, which occurs preferentially when the molecule resides in the membrane. All these properties, which we rationalized via optical spectroscopies and calculations, enable the effective eradication of Escherichia coli, with an inhibition concentration that is below that of current state-of-the-art treatments. Our approach holds significant potential for the development of new PS for controlling bacterial infections, particularly those caused by Gram-negative bacteria.
| S-EPMC10395270 | biostudies-literature
Project description:Metal-organic frameworks (MOFs) have been investigated recently in perovskite photovoltaics owing to their potential to boost optoelectronic performance and device stability. However, the impact of variations in the MOF side chain on perovskite characteristics and the mechanism of MOF/perovskite film formation remains unclear. In this study, three nanoscale thiol-functionalized UiO-66-type Zr-based MOFs (UiO-66-(SH)2 , UiO-66-MSA, and UiO-66-DMSA) are systematically employed and examined in perovskite solar cells (PSCs). Among these MOFs, UiO-66-(SH)2 , with its rigid organic ligands, exhibited a strong interaction with perovskite materials with more efficient suppression of perovskite vacancy defects. More importantly, A detailed and in-depth discussion is provided on the formation mechanism of UiO-66-(SH)2 -assisted perovskite film upon in situ GIWAXS performed during the annealing process. The incorporation of UiO-66-(SH)2 additives substantially facilitates the conversion of PbI2 into the perovskite phase, prolongs the duration of stage I, and induces a delayed phase transformation pathway. Consequently, the UiO-66-(SH)2 -assisted device demonstrates reduced defect density and superior optoelectronic properties with optimized power conversion efficiency of 24.09% and enhanced long-term stability under ambient environment and continuous light illumination conditions. This study acts as a helpful design guide for desired MOF/perovskite structures, enabling further advancements in MOF/perovskite optoelectronic devices.
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Project description:The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods: We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of "switch" on the photodynamic activity was studied in vitro. The in vivo mice with tumor model was applied to evaluate the "switch"-triggered enhanced photodynamic therapy efficacy. Results: A core-satellites structure with fluorescence off and on function was obtained when growing MnO2 on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO2 on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO2). Both the fluorescence and photodynamic activities can be turned off by MnO2 and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO2 significantly depleted the intracellular GSH via a MnO2 reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn2+ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion: This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes.
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Project description:A series of polyethyleneimine (PEI) incorporated MIL-101 adsorbents with different PEI loadings were reported for the first time in the present work. Although the surface area and pore volume of MIL-101 decreased significantly after loading PEI, all the resulting composites exhibited dramatically enhanced CO2 adsorption capacity at low pressures. At 100 wt% PEI loading, the CO2 adsorption capacity at 0.15 bar reached a very competitive value of 4.2 mmol g(-1) at 25°C, and 3.4 mmol g(-1) at 50°C. More importantly, the resulting adsorbents displayed rapid adsorption kinetics and ultrahigh selectivity for CO2 over N2 in the designed flue gas with 0.15 bar CO2 and 0.75 bar N2. The CO2 over N2 selectivity was up to 770 at 25°C, and 1200 at 50°C. We believe that the PEI based metal-organic frameworks is an attractive adsorbent for CO2 capture.
| S-EPMC3656390 | biostudies-literature
Project description:Two-dimensional covalent organic frameworks (2D-COFs) are crystalline, porous materials comprising aligned columns of π-stacked building blocks. With a view toward the application of these materials in organic electronics and optoelectronics, the construction of oligothiophene-based COFs would be highly desirable. The realization of such materials, however, has remained a challenge, in particular with respect to laterally conjugated imine-linked COFs. We have developed a new building block design employing an asymmetric modification on an otherwise symmetric backbone that allows us to construct a series of highly crystalline quaterthiophene-derived COFs with tunable electronic properties. Studying the optical response of these materials, we have observed for the first time the formation of a charge transfer state between the COF subunits across the imine bond. We believe that our new building block design provides a general strategy for the construction of well-ordered COFs from various extended building blocks, thus greatly expanding the range of applicable molecules.
| S-EPMC6400432 | biostudies-literature