Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

A novel EGFR inhibitor suppresses survivin expression and tumor growth in human gefitinib-resistant EGFR-wild type and -T790M non-small cell lung cancer.

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are currently used therapy for non-small cell lung cancer (NSCLC) patients; however, drug resistance during cancer treatment is a critical problem. Survivin is an anti-apoptosis protein, which promotes cell proliferation and tumor growth that highly expressed in various human cancers. Here, we show a novel synthetic compound derived from gefitinib, do-decyl-4-(4-(3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl) piper-azin-1-yl)-4-oxobutanoate, which is named as SP101 that inhibits survivin expression and tumor growth in both the EGFR-wild type and -T790M of NSCLC. SP101 blocked EGFR kinase activity and induced apoptosis in the A549 (EGFR-wild type) and H1975 (EGFR-T790M) lung cancer cells. SP101 reduced survivin proteins and increased active caspase 3 for inducing apoptosis. Ectopic expression of survivin by a survivin-expressed vector attenuated the SP101-induced cell death in lung cancer cells. Moreover, SP101 inhibited the gefitinib-resistant tumor growth in the xenograft human H1975 lung tumors of nude mice. SP101 substantially reduced survivin proteins but conversely elicited active caspase 3 proteins in tumor tissues. Besides, SP101 exerted anticancer abilities in the gefitinib resistant cancer cells separated from pleural effusion of a clinical lung cancer patient. Consistently, SP101 decreased the survivin proteins and the patient-derived xenografted lung tumor growth in nude mice. Anti-tumor ability of SP101 was also confirmed in the murine lung cancer model harboring EGFR T790M-L858R. Together, SP101 is a new EGFR inhibitor with inhibiting survivin that can be developed for treating EGFR wild-type and EGFR-mutational gefitinib-resistance in human lung cancers.

1550 nm excitation-responsive upconversion nanoparticles to establish dual-photodynamic therapy against pancreatic tumors.

The second near-infrared biological window b (NIR-IIb, 1500-1700 nm) is recently considered as the promising region for deeper tissue penetration. Herein, a nanocarrier for 1550 nm light-responsive dual-photodynamic therapy (PDT) is developed to efficiently boost singlet oxygen (1O2) generation. The dual-photosensitizers (PSs), rose bengal (RB) and chlorin e6 (Ce6), are carried by the silica-coated core-shell LiYbF4:Er@LiGdF4 upconversion nanoparticles (UCNPs), forming UCNP/RB,Ce6. Following 1550 nm laser irradiation, the upconversion emission of UCNP/RB,Ce6 in both green (∼550 nm) and red (∼670 nm) colors is fully utilized to activate RB and Ce6, respectively. The simultaneous triggering of dual-PS generates an abundant amount of 1O2 resulting in boosted PDT efficacy. This dual-PDT nanocarrier presents an enhanced anticancer effect under single dose treatment in comparison with the single-PS ones from in vitro and in vivo treatments. The marriage between the boosted dual-PDT and 1550 nm light excitation is anticipated to provide a new avenue for non-invasive therapy.

Enhancing Microcirculation on Multitriggering Manner Facilitates Angiogenesis and Collagen Deposition on Wound Healing by Photoreleased NO from Hemin-Derivatized Colloids.

A deficiency of nitric oxide (NO) supply has been found to impair wound healing. The exogenous topical delivery of NO is a promising approach to enhance vasodilation and stimulate angiogenesis and collagen deposition. In this study, the CN groups on the surface of Prussian blue (PB) nanocubes were carefully reduced to -CH2-NH2 to conjugate with COOH group of hemin consisting of a Fe-porphyrin structure with strong affinity toward NO. Accordingly, the NO gas was able to coordinate to hemin-modified PB nanocubes. The hemin-modified PB carrying NO (PB-NO) can be responsible to near-infrared (NIR) light (808 nm) exposure to induce the thermo-induced liberation of NO based on the light-to-heat transformation property of PB nanocubes. The NO supply on the incisional wound sites can be readily topically dropped the colloidal solution of PB-NO for receiving NIR light irradiation. The enhanced blood flow was in a controllable manner whenever the wound sites containing PB-NO received NIR light irradiation. The promotion of blood perfusion following the on-demand multidelivery of NO has effectively facilitated the process of wound closure to enhance angiogensis and collagen deposition.

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease.

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe3O4-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe3O4-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7 days compared to the non-treated leg that showed no evidence of the blood recovery.

Controllable CO Release Following Near-Infrared Light-Induced Cleavage of Iron Carbonyl Derivatized Prussian Blue Nanoparticles for CO-Assisted Synergistic Treatment.

Carbon monoxide (CO) causes the dysfunction of mitochondria to induce the apoptosis of cancer cells giving a promising choice as an emerging treatment. The currently reported CO-based complexes still suffer from many limitations. Synthesis of CO-release carriers in the manner of on-demand control is highly anticipated. In this study, we present a near-infrared (NIR) light-responsive CO-delivery nanocarrier, a PEGylated iron carbonyl derivatized Prussian blue (PB) nanoparticle (NP). Taking the structural characteristic containing Fe3+-N≡C-Fe2+ unit, the -CN- served as the active sites for the coordination of iron carbonyl, while the surface Fe sites chelated with the amine-functionalized polyethylene glycol (NH2-PEG6000-NH2) to yield PEGylated PB NPs carrying CO. The control of light intensity and exposure period is important to release the amount of CO as well as to deliver the hyperthermia effect. The combination therapy including CO and photothermal treatments displayed a synergistic effect against cancer cells. Importantly, the release of CO is inert in the blood circulation without NIR irradiation. The blood oxygen saturation measured by the pulse oximeter and the HCO3, tCO2, and pH values analyzed by the blood assay revealed the steady status from the mice studies, showing no acute CO poisoning.

Permeation of aromatic solvent mixtures through nitrile protective gloves.

The permeation of binary and ternary mixtures of benzene, toluene, ethyl benzene and p-xylene through nitrile gloves were investigated using the ASTM F739 test cell. The more slowly permeating component of a mixture was accelerated to have a shorter breakthrough time than its pure form. The larger differences in solubility parameter between a solvent mixture and glove resulted in a lower permeation rate. Solubility parameter theory provides a potential approach to interpret the changes of permeation properties for BTEX mixtures through nitrile gloves. Using a one-dimensional diffusion model based on Fick's law, the permeation concentrations of ASTM F739 experiments were appropriately simulated by the estimated diffusion coefficient and solubility. This study will be a fundamental work for the risk assessment of the potential dermal exposure of workers wearing protective gloves.