Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such “blocking and activating” enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.
The simultaneous entrapment of biological macromolecules and nanostructured silica-coated magnetite in sol-gel materials using a reverse-micelle technique leads to a bioactive, mechanically stable, nanometer-sized, and magnetically separable particles. These spherical particles have a typical diameter of 53 +/- 4 nm, a large surface area of 330 m(2)/g, an average pore diameter of 1.5 nm, a total pore volume of 1.427 cm(3)/g and a saturated magnetization (M(S)) of 3.2 emu/g. Peroxidase entrapped in these particles shows Michaelis-Mentan kinetics and high activity. The catalytic reaction will take place immediately after adding these particles to the reaction solution. These enzyme entrapping particles catalysts can be easily separated from the reaction mixture by simply using an external magnetic field. Experiments have proved that these catalysts have a long-term stability toward temperature and pH change, as compared to free enzyme molecules. To further prove the application of this novel magnetic biomaterial in analytical chemistry, a magnetic-separation immunoassay system was also developed for the quantitative determination of gentamicin. The calibration for gentamicin has a working range of 200-4000 ng/mL, with a detection limit of 160 ng/mL, which is close to that of the fluorescent polarization immunoassay (FPIA) using the same reactants.
Photodynamic therapy (PDT), which utilizes reactive oxygen species to kill cancer cells, has found wide applications in cancer treatment. However, the hypoxic nature of most solid tumors can severely restrict the efficiency of PDT. Meanwhile, the hydrophobicity and limited tumor selectivity of some photosensitizers also reduce their PDT efficacy. Herein, a photosensitizer‐Pd@Pt nanosystem (Pd@Pt‐PEG‐Ce6) is designed for highly efficient PDT by overcoming these limitations. In the nanofabrication, Pd@Pt nanoplates, exhibiting catalase‐like activity to decompose H2O2 to generate oxygen, are first modified with bifunctional PEG (SH‐PEG‐NH2). Then the Pd@Pt‐PEG is further covalently conjugated with the photosensitizer chlorin e6 (Ce6) to get Pd@Pt‐PEG‐Ce6 nanocomposite. The Pd@Pt‐PEG‐Ce6 exhibits good biocompatibility, long blood circulation half‐life, efficient tumor accumulation, and outstanding imaging properties. Both in vitro and in vivo experimental results clearly indicate that Pd@Pt‐PEG‐Ce6 effectively delivers photosensitizers to cancer cells/tumor sites and triggers the decomposition of endogenous H2O2 to produce oxygen, resulting in a remarkably enhanced PDT efficacy. Moreover, the moderate photothermal effect of Pd@Pt nanoplates also strengthen the PDT of Pd@Pt‐PEG‐Ce6. Therefore, by integrating the merits of high tumor‐specific accumulation, hypoxia modulation function, and mild photothermal effect into a single nanoagent, Pd@Pt‐PEG‐Ce6 readily acts as an ideal nanotherapeutic platform for enhanced cancer PDT.
The utility of employing a variable duty cycle pulsed plasma polymerization technique to control film chemistry during plasma depositions is examined using allyl alcohol as monomer gas. Large scale progressive variations in film composition are observed with sequential changes in the plasma duty cycles employed, all other plasma variables being held constant. In particular, the −OH functionality of the monomer is increasingly retained in the plasma generated thin films as the radio frequency duty cycle is lowered. Fourier transform infrared and X-ray photoelectron spectroscopic analyses of the films obtained reveal that excellent film chemistry control is achieved during plasma polymerization of this monomer. The surface density controllability of functional groups, coupled with a gradient layering technique described herein to improve film adhesion to substrate surfaces, provides ideal opportunities for molecular tailoring of surfaces via subsequent derivatization reactions.
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