Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

Continuous glucose monitoring(CGM)systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus.However,the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems.In this review,research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized.This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms.In each strategy,the various biocompatible layers on the biosensor surface,such as drug-releasing membranes,hydrogels,hydrophilic membranes,anti-biofouling membranes based on zwitterionic polymers,and bio-mimicking membranes,are described in detail.This review,therefore,provides researchers working on implantable biosensors for CGM systems with vital information,which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

Hypoxia-induced activity loss of a photo-responsive microtubule inhibitor azobenzene combretastatin A4

The conformation-dependent activity of azo-benzene combretastatin A4(Azo-CA4)provides a unique approach to reduce the side-effects of chemotherapy,due to the light-triggered conformation transition of its azobenzene moiety.Under hypoxic tumor microenviron-ment,however,the high expression of azoreductase can reduce azobenzene to aniline.It was postulated that the Azo-CA4 might be degraded under hypoxia,resulting in the decrease of its anti-tumor activity.The aim of this study was to verify such hypothesis in HeLa cells in vitro.The quantitative drug concentration analysis shows the ratio-metric formation of degradation end-products,confirming the bioreduction of Azo-CA4.The tubulin staining study indicates that Azo-CA4 loses the potency of switching off microtubule dynamics under hypoxia.Furthermore,the cell cycle analysis shows that the ability of Azo-CA4 to induce mitotic arrest is lost at low oxygen content.Therefore,the cytotoxicity of Azo-CA4 is compromised under hypoxia.In contrast,combretastatin A4 as a positive control maintains the potency to inhibit tubulin polymer-ization and break down the nuclei irrespective of light irradiation and oxygen level.This work highlights the influence of hypoxic tumor microenvironment on the anti-tumor potency of Azo-CA4,which should be considered during the early stage of designing translational Azo-CA4 delivery systems.

Curved carbon photo-oxygenation catalysts for the suppression and nanoscopic imaging ofβ-amyloid peptides fibrillation

The progression of Alzheimer’s disease(AD)is characterized with the deposition and aggregation ofβ-amyloid(Aβ).Visualizing Aβaggregates at high spatial resolution is beneficial for AD diagnosis and treatment.Herein,we designed a new molecule by conjugating corannulene(Cor)with rhodamine B isothiocyanate(Rhb),namely Cor-Rhb,for the nanoscopic imaging and modulating Aβpeptide fibrillation.The low duty cycle,high photon output and sufficient switching cycles enable Cor-Rhb suitable for localization-based nanoscopic fluorescence imaging.We find that Cor-Rhb can inhibit Aβpeptides fibrillization and interact directly with mature fibrils,triggering their disaggregation under light illumination.Noticeably reduced Aβ-mediated cytotoxicity after the addition of Cor-Rhb is also confirmed.These explorations suggest that Cor-Rhb displays great potential as a multifunctional therapeutic agent against amyloid-related diseases,and may largely facilitate a variety of super-resolution based biological applications.

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1:a mini-review

The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many tissues.NAD(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most cancers.Therefore,it could be a target for cancer therapy.Because it is a quinone reductase,many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose tumours.Its expression is higher in tumours than in normal tissues,and using target drugs such asβ-lapachone to reduce side effects in normal tissues can help.However,the physicochemical properties ofβlapachone limit its application.The problem can be solved by using nanosystems to deliverβ-lapachone.This minireview summarizes quinone-based fluorescent,nearinfrared and two-photon fluorescent probes,as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drugβ-lapachone.This review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

Hydroxyl radical-involved cancer therapy via Fenton reactions

The tumor microenvironment features over-expressed hydrogen peroxide(H_(2)O_(2)).Thus,versatile therapeutic strategies based on H_(2)O_(2) as a reaction substrate to generate hydroxyl radical(•OH)have been used as a prospective therapeutic method to boost anticancer efficiency.However,the limited Fenton catalysts and insufficient endogenous H_(2)O_(2) content in tumor sites greatly hinder•OH production,failing to achieve the desired therapeutic effect.Therefore,supplying Fenton catalysts and elevating H_(2)O_(2) levels into cancer cells are effective strategies to improve•OH generation.These therapeutic strategies are systematically discussed in this review.Furthermore,the challenges and future developments of hydroxyl radical-involved cancer therapy are discussed to improve therapeutic efficacy.

Phosphinic Acid/Nal Mediated Reductive Cyclization Approach for Accessing the L-1-Deoxynojirimycin Using a Two-Component Three-Centered (2C3C) Ugi Type Reaction

A catalytic two-component three-centered(2C3C)Ugi-type reaction was developed for the synthesis of L-1-deoxynojirimycin(DNJ)isomers using a chiron approach.This new and quite mild catalytic system,comprised of phenylphosphinic acid/Nal,was used to synthesize both the L-allo-DNJ and L-altro-DNJ in high yield.