A selective fluorescent turn-on probe for imaging and sensing of hydrogen peroxide in living cells.

Fluorescent turn-on probes have been extensively used in disease diagnosis and research on pathological disease mechanisms because of their low background interference. Hydrogen peroxide (H2O2) plays a vital role in regulating various cellular functions. In the current study, a fluorescent probe, HCyB, based on hemicyanine and arylboronate structures, was designed to detect H2O2. HCyB reacted with H2O2 and exhibited a good linear relationship for H2O2 concentrations ranging from 15 to 50 µM and good selectivity over other species. The fluorescent detection limit was 76 nM. Moreover, HCyB exhibited less toxicity and mitochondrial-targeting abilities. HCyB was successfully used to monitor exogenous or endogenous H2O2 in mouse macrophage RAW 264.7, human skin fibroblast WS1, breast cancer cell MDA-MB-231, and human leukemia monocytic THP1 cells.

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells.

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV-vis absorption peak was detected in the range of 700-1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur-Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231.

Boronates as hydrogen peroxide-reactive warheads in the design of detection probes, prodrugs, and nanomedicines used in tumors and other diseases.

Hydrogen peroxide (H2O2) has always been a topic of great interests attributed to its vital role in biological process. H2O2 is known as a major reactive oxygen species (ROS) which is involve in numerous physiological processes such as cell proliferation, signal transduction, differentiation, and even pathogenesis. A plenty of diseases development such as chronic disease, inflammatory disease, and organ dysfunction are found to be relevant to abnormality of H2O2 production. Thus, imminent and feasible strategies to modulate and detect H2O2 level in vitro and in vivo have gained great importance. To date, the boronate-based chemical structure probes have been widely used to address the problems from the above aspects because of the rearranged chemical bonding which can detect and quantify ROS including hydrogen peroxide (H2O2) and peroxynitrite (ONOO-). This present article discusses boronate-based probes based on the chemical structure difference as well as reactivities to H2O2 and ONOO-. In this review, we also focus on the application of boronate-based probes in the field of cell imaging, prodrugs nanoplatform, nanomedicines, and electrochemical biosensors for disease diagnosis and treatment. In a nutshell, we outline the recent application of boronate-based probes and represent the prospective potentiality in biomedical domain in the future.

Synthesis of a Multifunctional Glyco-Block Copolymer through Reversible Addition-Fragmentation Chain Transfer Polymerization and Click Chemistry for Enzyme and Drug Loading into MDA-MB-231 Cells.

Reversible addition-fragmentation chain transfer polymerization has been used in various applications such as preparing nanoparticles, stimulus-responsive polymers, and hydrogels. In this study, the combination of this polymerization method and Cu(I)-catalyzed azide-alkyne cycloaddition click chemistry was used to prepare the multifunctional glyco-diblock copolymer P(PEG-co-AM)-b-PF, which is composed of mannosides for cell targeting, poly(ethylene glycol) (PEG) for biocompatibility, and aryl-aldehyde moieties for enzyme immobilization. The alkyne group in the polymer structure enables the alternation for other azide-conjugated monomers. The stepwise synthesis of the polymers was fully characterized. P(PEG-co-AM)-b-PF was self-assembled into polymeric nanoparticles (BDOX-GOx@NPs) for glucose oxidase immobilization through Schiff base formation and for encapsulating the prodrug of arylboronate-linked doxorubicin (BA-DOX) under optimal conditions. Glucose oxidase in BDOX-GOx@NPs catalyzes glucose oxidation to produce gluconic acid and H2O2, which cause oxidative stress. Glucose oxidase also consumes glucose, causing starvation in cancer cells. The produced H2O2 can selectively activate the anticancer prodrug BA-DOX for chemotherapy. In vitro data indicate that GOx and the prodrug BA-DOX present inside BDOX-GOx@NPs exhibit higher stability than free glucose oxidase with a favorable active DOX release profile. MDA-MB-231 cells, which express mannose receptors, were used to establish a model in this study. The bioactivity of the nanoplatform in the two- and three-dimensional models of MDA-MB-231 cancer cells was investigated to ascertain its antitumor efficacy.

Design and Application of a Flexible Blood Oxygen Sensing Array for Wearable Devices.

The performance of portable or wearable oximeters is affected by improper movement or wear, which causes an error in the blood oxygen concentration calculation. The error comes from external incident stray light or light leakage caused by the improper fit of the sensor to the skin. This study aimed to develop a flexible blood oxygen sensing system with a 3 × 3 array that uses a reflective-type blood oxygen sensing chip to sequentially measure the blood oxygen levels at nine locations through a time division pulse modulation method. Each sensing chip has light transmission and receiving parts. A flip chip package was used to integrate the sensing chip, and a flexible parylene substrate that could fit the curvature of the wrist and locate the array of photo diodes around the radial artery of the wrist was used. By scanning the sensor array in dynamic behavior, the correct light intensity can be extracted to obtain the blood oxygen concentration and prevent errors due to improper fit or sensor movement during exercise.

Synthesis of Multi-Functional Nano-Vectors for Target-Specific Drug Delivery.

Magnetic nanoparticles have gained attention in cancer therapy due to their non-toxic properties and high bio-compatibility. In this report, we synthesize a dual-responsive magnetic nanoparticle (MNP) that is sensitive to subtle pH and temperature change as in the tumor microenvironment. Thus, the functional doxorubicin (DOX)-loaded MNP (DOX-PNIPAM-PMAA@Fe3O4) can perform specific DOX releases in the cancer cell. The particle was characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta-potential, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The microscopy data revealed the particle as having a spherical shape. The zeta-potential and size distribution analysis data demonstrated the difference for the stepwise modified MNPs. The FTIR spectrum showed characteristic absorption bands of NH2-SiO2@Fe3O4, CPDB@Fe3O4, PMAA@Fe3O4, and PNIPAM-PMAA@Fe3O4. Drug-loading capacity and releasing efficiency were evaluated under different conditions. Through an in vitro analysis, we confirmed that PNIPAM-PMAA@Fe3O4 has enhanced drug releasing efficiency under acidic and warmer conditions. Finally, cellular uptake and cell viability were estimated via different treatments in an MDA-MB-231 cell line. Through the above analysis, we concluded that the DOX-loaded particles can be internalized by cancer cells, and such a result is positive and prospective.

Lectin-Triggered Aggregation of Glyco-Gold Nanoprobes for Activity-based Sensing of Hydrogen Peroxide by the Naked Eye.

The purpose of this study was to develop a colorimetric assay for detecting hydrogen peroxide (H2 O2 ) through a combination of using an aryl boronate (AB) derivative and gold nanoparticles (AuNPs). The unique optical property of AuNPs is applied to design a detection probe. The aggregation of AuNPs could be directly observed as a color change by the naked eye. A mannoside-boronate-sulfide (MBS) ligand was designed that contains an arylboronate (AB), a mannoside, and a thiol group. The thiol group bonds covalently with the surface of AuNPs to obtain MBS@AuNPs. The mannoside moiety recognizes concanavalin A (Con A), a lectin with four carbohydrate recognition sites that can specifically recognize the non-reducing end of an α-D-mannoside or α-D-glucoside structure. The AB structure on MBS first reacts with H2 O2 and then inserts an oxygen atom in the B-H bond, which triggers intramolecular electron rearrangement to cleave the covalent bond, resulting in a MBSt mixture. The MBS or MBSt is then modified to citrate-coated AuNPs (c-AuNPs) to have MBS@AuNPs or MBSt@AuNPs. When the MBS@AuNPs are incubated with Con A, the Con A recognizes multiple mannosides on the surface of the MBS@AuNPs. Subsequently, the MBS@AuNPs aggregate and the solution's color changes from red to purple, but this color change does not occur in the case of MBSt@AuNPs. The phenomenon can be observed by the naked eye.