Zwitterionic Hydrogel Coating with Antisediment Properties for Marine Antifouling Applications.

Biofouling is a serious issue affecting the marine industry because the attached micro- and macrocontaminants can increase fuel consumption and damage ship hulls. A hydrophilic hydrogel-based coating is considered a promising antifouling material because it is environmentally friendly and the dense hydration layer can protect the substrate from microbial attachment. However, sediment adsorption can be an issue for hydrogel-based coatings. Their natural soft and porous structures can trap sediment from the marine environment and weaken the antifouling capability. There is still little research on the antisediment properties of hydrogels, and none of them deal with this problem. Here, we report on optimizing zwitterionic hydrogel-based coatings to improve their antisediment properties and achieve comparable performance to commercial biocidal coatings, which are the gold standard in the antifouling coating area. After 1 week of sediment contamination and 2 weeks of diatom coculturing, this optimized zwitterionic hydrogel coating maintained its antifouling properties with a few diatoms on the surface. Its large-scale samples also achieved antifouling performance similar to that of biocidal coatings in the Atlantic Ocean for 1.5 months. More importantly, our research provides a universal strategy to improve the antisediment properties of soft hydrogel-based coatings. For the first time, we report that the introduction of interfacial electrostatic interactions enhanced the antisediment properties of hydrogels.

Recent advances in oral insulin delivery technologies.

With the rise in diabetes mellitus cases worldwide, oral delivery of insulin is preferred over subcutaneous insulin administration due to its good patient compliance and non-invasiveness, simplicity, and versatility. However, oral insulin delivery is hampered by various gastrointestinal barriers that result in low drug bioavailability and insufficient therapeutic efficiency. Numerous strategies have been developed to overcome these barriers and increase the bioavailability of oral insulin. Yet, no commercial oral insulin product is available to address all clinical hurdles because of various substantial obstacles related to the structural organization and physiological function of the gastrointestinal tract. Herein, we discussed the significant physiological barriers (including chemical, enzymatic, and physical barriers) that hinder the transportation and absorption of orally delivered insulin. Then, we showcased recent significant and innovative advances in oral insulin delivery technologies. Finally, we concluded the review with remarks on future perspectives on oral insulin delivery technologies and potential challenges for forthcoming clinical translation of oral insulin delivery technologies.

An injectable and biodegradable zwitterionic gel for extending the longevity and performance of insulin infusion catheters.

Continuous subcutaneous insulin infusion (CSII) is an essential insulin replacement therapy in the management of diabetes. However, the longevity of clinical CSII is limited by skin complications, by impaired insulin absorption and by occlusions associated with the subcutaneous insertion of CSII catheters, which require replacement and rotation of the insertion site every few days. Here we show that a biodegradable zwitterionic gel covering the tip end of commercial off-the-shelf CSII catheters fully resolves early skin irritations, extends the longevity of catheters and improves the rate of insulin absorption (also with respect to conventional syringe-based subcutaneous injection) for longer than 6 months in diabetic mice, and by 11 days in diabetic minipigs (from 2 to 13 days, under standard CSII-wearing conditions of insulin pump therapy and in a continuous basal-plus-bolus-infusion setting). The implanted gel displayed anti-inflammatory and anti-foreign-body-reaction properties and promoted the local formation of new blood vessels. The gel is subcutaneously injected before the tip of catheter is inserted into it, and should be generally applicable to CSII catheters and other implantable devices.

Using Bacillus thuringiensis HM-311@hydroxyapatite@biochar beads to remediate Pb and Cd contaminated farmland soil.

Cadmium (Cd) and lead (Pb) have become serious soil contaminants in China. In this work, we immobilized B. thuringiensis HM-311 (a heavy metal resistant strain) using vinegar residue biochar and hydroxyapatite (HAP) to form BtHM-311@HAP@biochar calcium alginate beads. In aqueous solution, the beads respectively reduced 1000 mg/L Pb2+ to 14.59 mg/L and 200 mg/L Cd2+ to 5.40 mg/L within 20 h. Furthermore, the results of pot experiment showed that the BtHM-311@HAP@biochar beads reduced the bioavailability of Pb and Cd in soil. The accumulation of Pb2+ in rice decreased by 39.97% in shoots and 46.40% in roots, while that of Cd2+ decreased by 34.59 and 44.9%, respectively. Similarly, the accumulation of Pb2+ in corn decreased by 40.86% in shoots and 51.34% in roots, while that of Cd2+ decreased by 41.28 and 42.91%, respectively. The beads also increased the microbial community diversity in the rhizosphere soil. These findings indicate that BtHM-311@HAP@biochar beads may be applicable for the bioremediation of Cd- and Pb-contaminated farmland soil.

Polymeric PD-L1 blockade nanoparticles for cancer photothermal-immunotherapy.

Checkpoint inhibitors, such as antibodies blocking the PD-1/PD-L1 pathway, are among the most promising immunotherapies to treat metastatic cancers, but their response rate remains low. In addition, the usage of monoclonal antibodies as checkpoint inhibitors is associated with a series of drawbacks. Herein, an all synthetic nanoparticle with PD-L1 blockade capability is developed for cancer photothermal-immunotherapy. The polymeric nanoparticle integrates photothermal treatment, antitumor vaccination, and PD-1/PD-L1 blockade in a single system to augment the antitumor efficacy. In a CT26 bilateral tumor model, intravenously injected nanoparticles accumulate in tumor sites and mediate strong photothermal effects, eradicate the NIR treated primary tumors and elicit strong antitumor immunity by inducing immunogenic cell death (ICD). Growth of the untreated distant tumors is also suppressed due to the synergies of systemic antitumor immune activation and PD-L1 blockade. Our strategy offers a simple but promising approach for the treatment of metastatic cancer.

Biodegradable Zwitterionic Cream Gel for Effective Prevention of Postoperative Adhesion.

Postoperative peritoneal adhesions were frequent complications for almost any types of abdominal and pelvic surgery. This led to numerous medical problems and huge financial burden to the patients. Current anti-adhesion strategies focused mostly on physical barriers including films and hydrogels. However, they can only alleviate or reduce adhesions to certain level and their applying processes were far from ideal. This work reported the development of a biodegradable zwitterionic cream gel presenting a series of characters for an idea anti-adhesion material, including unique injectable yet malleable and self-supporting properties, which enabled an instant topical application, no curing, waiting or suturing, no hemostasis requirement, protein/cell resistance and biodegradability. The cream gel showed a major advancement in anti-adhesion efficacy by completely and reliably preventing a primary and a more severe recurrent adhesion in rat models.

Fouling-resistant zwitterionic polymers for complete prevention of postoperative adhesion.

Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the "nonfouling" zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our "complete prevention" approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.

Zwitterionic micelles efficiently deliver oral insulin without opening tight junctions.

Oral delivery of protein drugs is considered a life-changing solution for patients who require regular needle injections. However, clinical translation of oral protein formulations has been hampered by inefficient penetration of drugs through the intestinal mucus and epithelial cell layer, leading to low absorption and bioavailability, and safety concerns owing to tight junction openings. Here we report a zwitterionic micelle platform featuring a virus-mimetic zwitterionic surface, a betaine side chain and an ultralow critical micelle concentration, enabling drug penetration through the mucus and efficient transporter-mediated epithelial absorption without the need for tight junction opening. This micelle platform was used to fabricate a prototype oral insulin formulation by encapsulating a freeze-dried powder of zwitterionic micelle insulin into an enteric-coated capsule. The biocompatible oral insulin formulation shows a high oral bioavailability of >40%, offers the possibility to fine tune insulin acting profiles and provides long-term safety, enabling the oral delivery of protein drugs.

Engineering and Application Perspectives on Designing an Antimicrobial Surface.

Infections, contaminations, and biofouling resulting from micro- and/or macro-organisms remained a prominent threat to the public health, food industry, and aqua-/marine-related applications. Considering environmental and drug resistance concerns as well as insufficient efficacy on biofilms associated with conventional disinfecting reagents, developing an antimicrobial surface potentially improved antimicrobial performance by directly working on the microbes surrounding the surface area. Here we provide an engineering perspective on the logic of choosing materials and strategies for designing antimicrobial surfaces, as well as an application perspective on their potential impacts. In particular, we analyze and discuss requirements and expectations for specific applications and provide insights on potential misconnection between the antimicrobial solution and its targeted applications. Given the high translational barrier for antimicrobial surfaces, future research would benefit from a comprehensive understanding of working mechanisms for potential materials/strategies, and challenges/requirements for a targeted application.

Biomaterial-tight junction interaction and potential impacts.

The active pharmaceutical ingredients (APIs) have to cross the natural barriers and get into the blood to impart the pharmacological effects. The tight junctions (TJs) between the epithelial cells serve as the major selectively permeable barriers and control the paracellular transport of the majority of hydrophilic drugs, in particular, peptides and proteins. TJs perfectly balance the targeted transport and the exclusion of other unexpected pathogens under the normal conditions. Many biomaterials have shown the capability to open the TJs and improve the oral bioavailability and targeting efficacy of the APIs. Nevertheless, there is limited understanding of the biomaterial-TJ interactions. The opening of the TJs further poses the risk of autoimmune diseases and infections. This review article summarizes the most updated literature and presents insights into the TJ structure, the biomaterial-TJ interaction mechanism, the benefits and drawbacks of TJ disruption, and methods for evaluating such interactions.

Liquid-crystal based Fabry-Perot interferometer displacement sensor.

A Fabry-Perot interferometer displacement sensor is proposed and demonstrated. This sensor is prepared by inserting two ceramic ferrules into a polydimethylsiloxane (PDMS) hose to generate a Fabry-Perot cavity. The cavity is filled with nematic liquid crystals (NLCs), which induce a Vernier effect due to the birefringence of NLCs. The flexible PDMS hose makes the cavity length adjustable. A displacement sensor with sensitivity of ∼2.97 nm/µm and a dynamic range of 0.9 mm at the center wavelength of 1550 nm is experimentally demonstrated.

Phosphorescent cationic iridium(iii) complexes dynamically bound to cyclodextrin vesicles: applications in live cell imaging.

We report cationic Ir(iii) complexes functionalized with adamantyl groups designed to bind to ß-cyclodextrin vesicles (CDV) with high affinity (K a = 1 × 106 M-1). The emission of the complexes is tuned by changing the nature of the cyclometalating ligands. The host-guest adduct of CDV and Ir(iii) complexes shows increased and significantly blue-shifted emission due to the lower mobility of the Ir(iii)-complexes residing in the less polar environment of the vesicle surface. Ir(iii)-decorated CDV are efficiently taken up by cells and can be used in live cell imaging. The CDV act as carriers to transport the phosphorescent complexes into cells where they selectively stain mitochondria.

Unexpected isocyanide-based cascade cycloaddition reaction with methyleneindolinone.

An unprecedented cascade reaction of isocyanide and methyleneindolinone has been established, which represents a novel and different reaction mode. This present transformation involves the ring-opening of methyleneindolinone and the construction of two other new rings simultaneously in an atom-economic manner.