Copper-Doped Platinum/Metal-Organic Framework Nanostructures for Imaging-Guided Photothermal and H₂O₂ Self-Supplying Photodynamic/Photothermal/Chemodynamic Therapy

Simultaneous photodynamic/photothermal therapy (PDT/PTT) is a combination cancer treatment that combines the principles of both PDT and PTT to achieve an effective and comprehensive attack on cancer cells. However, both approaches require an external light source to generate reactive oxygen species (ROS) and thermal heat, which could potentially hinder the therapeutic efficacy due to the low tissue penetration of light in vivo. Chemodynamic therapy (CDT) is a type of therapy that uses the ROS generated by the chemical reaction between a prodrug and a catalyst to kill cancer cells. We developed a combination therapy of three modalities (PTT/PDT/CDT) using the metal-organic framework (MOF). The Cu2+-doped MOF PCN-224 nanostructures modified with platinum (Pt) cluster and folic acid (FA) provided excellent tumor targeting, photothermal conversion ability, and ROS generated by the Pt cluster and Cu2+ under 650 nm light irradiation. Moreover, this multimodel nanocomposite had an extremely low dark toxicity but excellent phototoxicity under the combination laser irradiation at 650 nm, both in vitro and in vivo. Therefore, our prepared folic acid-conjugated PCN-224/Pt/Cu2+ (FA-PPC) nanosphere could be applied as a very promising multimodal phototherapeutic agent for enhanced cancer therapy in future clinical applications

Additional file 1 of NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

Additional file 1: Figure S1. (a) Hydrodynamic diameter of APCZ within 14-day dialysis in PBS buffer (pH 7.4). (b) Zeta potentials of aqueous APCZ dispersion before and after 14 day’s dialysis in PBS buffer (pH 7.4). Data shown as mean ± SD, n = 3 per treatment. Figure S2. (a) UV–vis absorption spectra of AIPH at various concentrations. (b) Standard curve of AIPH determined from (a) at 364 nm. Figure S3. UV–vis absorption spectra of AIPH before and after loading (solutions were diluted 5-fold for measurements). Figure S4. Photothermal curves of aqueous PDA (48.16 µg mL−1) and PVP-CuS (22.78 µg mL−1) dispersions exposed to a 1064 nm laser (1.0 W cm−2, 10 min). Figure S5. UV–vis absorption spectra of DTNB at various concentrations (10 −50 µM). Figure S6. (a) UV–vis absorption spectra of DTNB (25 µM) with various concentrations of GSH (12.5, 25, 37.5, and 50 µM). (b) Standard curve determined from (a) at 412 nm. Figure S7. Detection of GSH (50 µM) depletion by various concentrations of AP dispersions (5, 10, 15, 20 and 25 µg mL−1) after 12 h of reaction. [DTNB] = 25 µM. Figure S8. The degradation of AP in GSH, acid (pH 5.0) and acidic GSH (pH 5.0) for 12 h. [GSH] = 1 mM, [AP] = 100 µg mL−1. Figure S9. Detection of GSH (50 µM) depletion by aqueous CuCl2 (50 µM) solution for 10, 30, 60, 120, 180, 240 and 360 min, respectively. [DTNB] = 25 µM. Figure S10. UV–vis absorption spectra of PVP-CuS (25 µg mL−1) after incubation with various concentrations of GSH (0, 1, 2, 4 and 10 mM) for 6 h. Figure S11. Digital photos of PVP-CuS/GSH mixtures (separated by centrifugation and re-dispersed in 400 µL of DI H2O) after 6 h of reaction. [PVP-CuS] = 25 µg mL−1, [GSH] = (1) 0 mM, (2) 1 mM, (3) 2 mM, (4) 4 mM and (5) 10 mM. Figure S12. Relative Cu ions release from PVP-CuS/GSH mixtures after incubation for 6 h. [PVP-CuS] = 25 µg mL−1, [GSH] = 1, 2, 4 and 10 mM. Figure S13. TEM images of (a) PVP-CuS and (b-f) PVP-CuS/GSH mixtures after 24 h of reaction. [PVP-CuS] = 25 µg mL−1, [GSH] = 10 mM. Figure S14. Cumulative AIPH release profile of APCZ in PBS buffer of pH 7.4, pH 7.4 + GSH (10 mM), pH 5.0 and pH 5.0 + GSH (10 mM) for 24 h. Data shown as mean ± SD, n = 3 per treatment. Figure S15. Cumulative Cu ions release profile of APCZ in PBS buffer of pH 7.4, pH 7.4 + GSH (10 mM), pH 7.4 + GSH (10 mM) + Laser, pH 5.0, pH 5.0 + GSH (10 mM) and pH 5.0 + GSH (10 mM) + Laser. The orange arrows represented laser (1064 nm, 1.0 W cm−2) treatment, each time point was radiated for 10 min. Data shown as mean ± SD, n = 3 per treatment. Figure S16. UV–vis−NIR absorption spectra of APCZ and APCZ/GSH mixture after incubation in aqueous ABTS solution (44 °C) for 6 h. [APCZ] = 400 µg mL−1, [GSH] = 0.5 mM, [ABTS] = 20 µg mL−1. Figure S17. IC50 of PCZ group in normoxic condition calculated from MTT results by GraphPad Prism 8 software. Figure S18. (a) The blood clearance kinetics of APCZ after intravenously administration. (b) Biodistribution analysis of APCZ in 4T1 tumor bearing mice after the tail vein injection for 24 and 48 h. Data shown as mean ± SD, n = 3 per treatment. Figure S19. Standard curves of (a) mouse TNF-α and (b) mouse IFN-γ. O.D. means optical density (absorbance at 450 nm). (c) TNF-α and (d) IFN-γ levels in sera isolated from different groups after 7-day treatments. Data shown as mean ± SD, n = 3 per treatment. Statistical significance was set at *p < 0.05, **p < 0.01, ***p < 0.001. Figure S20. H&E staining images of major organs after different treatments. Scale bars = 50 μm. Table S1. IC50 of different groups calculated from MTT results by GraphPad Prism 8 software

Porphyrinic Metal–Organic Framework PCN-224 Nanoparticles for Near-Infrared-Induced Attenuation of Aggregation and Neurotoxicity of Alzheimer’s Amyloid‑β Peptide

The aberrant aggregation of amyloid-β peptide (Aβ) in the brain has been considered as the major pathological hallmark of Alzheimer’s diseases (AD). Inhibition of Aβ aggregation is considered as an attractive therapeutic intervention for alleviating amyloid-associated neurotoxicity. Here, we report the near-infrared light (NIR)-induced suppression of Aβ aggregation and reduction of Aβ-induced cytotoxicity via porphyrinic metal–organic framework (MOF) PCN-224 nanoparticles. PCN-224 nanoparticles are hydrothermally synthesized by coordinating tetra-kis­(4-carboxyphenyl)­porphyrin (TCPP) ligands with zirconium. The PCN-224 nanoparticles show high photo-oxygenation efficiency, good biocompatibility, and high stability. The study reveals that the porphyrinic MOF-based nanoprobe activated by NIR light could successfully inhibit self-assembly of monomeric Aβ into a β-sheet-rich structure. Furthermore, photoexcited PCN-224 nanoparticles also significantly reduce Aβ-induced cytotoxicity under NIR irradiation

Ultrasmall Metal–Organic Framework Zn-MOF-74 Nanodots: Size-Controlled Synthesis and Application for Highly Selective Colorimetric Sensing of Iron(III) in Aqueous Solution

Here, a novel colorimetric sensing platform for highly selective detection of Fe³⁺ in aqueous solutions was developed based on zero-dimensional Zn-MOF-74 [Zn₂(DOBDC), DOBDC = 2,5-dihydroxyterephthalic acid] nanodots. The first ultrasmall Zn-MOF-74 nanodots with the average size within 10 nm were successfully synthesized by manipulating the initial conditions with a diluted material system. It was found that the ultrasamll MOF nanodots had a highly selective interaction with Fe³⁺ and showed a specific blue colorimetric change in aqueous solution. The highly dispersive nature in aqueous solution and high surface-to-volume ratio help MOF-74 nanodots closely interact with the targeted Fe³⁺ ions with a low limit of detection of 1.04 μM and a fast response within seconds. Finally, we demonstrate that the selective Fe³⁺ sensing mechanism of Zn-MOF-74 nanodots is due to the selective framework disruption and the formation of Fe-DOBDC salt complex with blue color. It is the first report of nanoscale MOF based colorimetric Fe³⁺ sensor with low limit of detection (LOD) comparable even to fluorescent MOF based Fe³⁺ sensors, which could be easily observed by naked-eye without expensive fluorescence apparatuses. The good colorimetric stability in aqueous environment, low limit of detection, rapid response, and nanosize nature enable this MOF nanodot to be a good Fe³⁺ sensing probe for biological and environmental sensing applications