Unraveling Intracellular Protein Corona Components of Nanoplastics via Photocatalytic Protein Proximity Labeling.

Bioaccumulation of nanoplastic particles has drawn increasing attention regarding environmental sustainability and biosafety. How nanoplastic particles interact with the cellular milieu still remains elusive. Herein, we exemplify a general approach to profile the composition of a "protein corona" interacting with nanoparticles via the photocatalytic protein proximity labeling method. To enable photocatalytic proximity labeling of the proteome interacting with particles, iodine-substituted BODIPY (I-BODIPY) is selected as the photosensitizer and covalently conjugated onto amino-polystyrene nanoparticles as a model system. Next, selective proximity labeling of interacting proteins is demonstrated using I-BODIPY-labeled nanoplastic particles in both Escherichia coli lysate and live alpha mouse liver 12 cells. Mechanistic studies reveal that the covalent modifications of proteins by an aminoalkyne substrate are conducted via a reactive oxygen species photosensitization pathway. Further proteomic analysis uncovers that mitochondria-related proteins are intensively involved in the protein corona, indicating substantial interactions between nanoplastic particles and mitochondria. In addition, proteostasis network components are also identified, accompanied by consequent cellular proteome aggregation confirmed by fluorescence imaging. Together, this work exemplifies a general strategy to interrogate the composition of the protein corona of nanomaterials by endowing them with photooxidation properties to enable photocatalytic protein proximity labeling function.

Hydrophobically Modified Cellulose Nanofibers-Enveloped Solid Lipid Microparticles for Improved Antioxidant Cargo Retention.

This study introduces a cellulose nanofiber surfactant system, in which the surface is hydrophobically modified with different alkyl chain structures for the effective envelopment of solid lipid microparticles (SLMs). To endow bacterial cellulose nanofibers (BCNFs) with excellent ability to assemble at the lipid-water interface, alkyl chains with designated molecular structures, such as decane, didecane, and eicosane, are covalently grafted onto the BCNF surface. Interfacial tension and interfacial rheology measurements indicate that dialkyl chain-grafted BCNFs (diC10 BCNF) exhibit strong interfibrillar association at the interface. The formation of a dense and tough fibrillary membrane contributes significantly to the enveloping of the SLMs, regardless of the lipid type. Because the diC10 BCNF-enveloped SLMs exhibit a core molecular crystalline phase at the microscale, they can immobilize an oil-soluble antioxidant while maintaining its long-term storage stability. These findings show that the cellulose-surfactant-based SLM technology is applicable to the stabilization and formulation of readily denatured active ingredients.

Molecular Docking-Guided Design on Glucose-Responsive Nanoparticles for Microneedle Fabrication and "Three-Meal-per-Day" Blood-Glucose Regulation.

It was greatly significant, but difficult, to develop stimulus-responsive polymeric nanoparticles with efficient protein-loading and protein-delivering properties. Crucial obstacles were the ambiguous protein/nanoparticle-interacting mechanisms and the corresponding inefficient trial-and-error strategies, which brought large quantities of experiments in design and optimization. In this work, a molecular docking-guided universal "segment-functional group-polymer" process was proposed to simplify the previous laborious experimental step. The insulin-delivering glucose-responsive polymeric nanoparticles for diabetic treatments were taken as the examples. The molecular docking study obtained insights from the insulin/segment interactions. It was then experimentally confirmed in six functional groups for insulin-loading performances of their corresponding polymers. The optimization formulation was further proved effective in blood-glucose stabilization on the diabetic rats under the "three-meal-per-day" mode. It was believed that the molecular docking-guided designing process was promising in the protein-delivering field.

Tough adhesion enhancing strategies for injectable hydrogel adhesives in biomedical applications.

Injectable hydrogel adhesives have gained widespread attention due to their ease of use, fast application time, and suitability for minimally invasive procedures. Several biomedical applications depend on tough adhesion between hydrogel adhesives and tissues, including wound closure and healing, hemostasis, tissue regeneration, drug delivery, and wearable electronic devices. Compared with bulk hydrogel adhesives formed ex situ, injectable hydrogel adhesives are more difficult to achieve strong adhesion strength due to a further balance of cohesion and adhesion while maintaining their flowability. In this review, the critical principles in designing tough adhesion of injectable hydrogel adhesives are summarized, including simultaneously enhancing their intrinsic interfacial toughness (Γ0inter) and mechanical dissipation (ΓDinter). Thereafter, various design strategies to enhance the Γ0inter and ΓDinter are discussed and evaluated respectively, involving multiple noncovalent/covalent interactions, topological connections, and polymer network structures. Furthermore, targeted biomedical applications of injectable hydrogel adhesives for specific tissue needs are systematically highlighted. In the end, this review outlines the challenges and trends in producing next-generation multifunctional injectable hydrogels for both practical and translational applications.

Glucose-responsive nanoparticles designed via a molecular-docking-driven method for insulin delivery.

Nocturnal blood glucose regulation was one of the key challenges in diabetic treatments. However, development of the smart insulin complexes with mild and glucose-responsive delivering performances was mostly relied on experience of the senior researchers and numerous confirmation experiments. In this work, a series of bioinspired fatty-acid-modified glucose-responsive insulin-delivering polymeric nanoparticles were designed. The molecular docking technique was utilized to efficiently screen the fatty-acid-derived functional groups. The results provided the basis for polymer functionalization and simplified the optimization experiments. For the optimized formulation (C10MS), insulin-loaded C10MS successfully fulfilled the nocturnal-glycemic-controlling requirement of the diabetic rats with lower occurrence of hypoglycemia than the conventional insulin injection schemes. Such formulation also possessed good biocompatibility with the moderate elimination kinetics in vivo, which matched the demand of bio-safety in the daily treatments. Overall, this work opened up a new path for efficient design of functional polymeric materials.

Polyphosphazene and Non-Catechol-Based Antibacterial Injectable Hydrogel for Adhesion of Wet Tissues as Wound Dressing.

Wound dressings with excellent adhesiveness, antibacterial, self-healing, hemostasis properties, and therapeutic effects have great significance for the treatment of acute trauma. So far, numerous mussel-inspired catechol-based wet adhesives have been reported, opening a pathway for the treatment of acute trauma. However, catechol-based hydrogels are easily oxidized, which limits their applications. Here, the design of a polyphosphazene and non-catechol based antibacterial injectable hydrogel is reported as a multifunctional first aid bandage. Inspired by barnacle cement proteins, a series of dynamic phenylborate ester based adhesive hydrogels are prepared by combining the cation-π structure modified polyphosphazene with polyvinyl alcohol. The inherent antibacterial property (4 h antibacterial rate 99.6 ± 0.2%), anti-mechanical damage, and hemostatic behavior are investigated to confirm multi-functions of wound dressings. In water, the hydrogels firmly adhere to tissue surfaces through cation-π and π-π interactions as well as hydrogen bonding (adhesion strength = 45 kPa). Moreover, in vivo experiments indicate the hydrogels can shorten the bleeding time and reduce the amount of bleeding by 88%, and significantly accelerate the wound healing rate. These hydrogels have a promising application in the treatment of acute trauma, which is in urgent need of anti-infection and hemostasis.

Recent research progress on polyphosphazene-based drug delivery systems.

In recent years, synthetic polymer materials have become a research hotspot in the field of drug delivery. Compared with natural polymer materials, synthetic polymer materials have more flexible structural adjustability, and can be designed to obtain clinically required delivery vehicles. Polyphosphazenes are one of the most promising biomedical materials in the future due to their controllable degradation properties and structural flexibility. These materials can be designed by controlling the hydrophilic and hydrophobic balance, introducing functional groups or drugs to form different forms of administration, such as nanoparticles, polyphosphazene-drug conjugates, injectable hydrogels, coatings, etc. In addition, the flexible backbone of polyphosphazenes and the flexibility of substitution enable them to meet researchers' design requirements in terms of stereochemistry, nanostructures, and topologies. At present, researchers have achieved a lot of successful practices in the field of targeted delivery of anticancer drugs/proteins/genes, bone tissue engineering repair, cell imaging tracking, photothermal therapy, and immunologic preparations. This review provides a summary of the progress of the recent 10 years of polyphosphazene-based drug delivery systems in terms of of chemical structure and functions.

Co-firing of levator palpebrae and masseter muscles links the masticatory and oculomotor system in humans.

Simultaneous co-firing of the levator palpebrae (LP) and pterygoid muscles were recorded in Marcus Gann Syndrome (MGS) patients in early clinical studies. "Release hypothesis" proposed an intrinsic masticatory oculomotor neural circuit and this kind circuit, which, however, has been observed only in amphibian. On the other hand, congenital miswiring hypothesis has overwhelmed other interpretations. However, the same phenomenon visualized in MGS cases was unveiled in human subjects without any sign of congenital oculomotor disorder. To further study co-firing of the upper eyelid and jaw muscles, we applied non-invasive EMG recording of the upper eyelid and ipsilateral masseter muscle belly in nine healthy volunteers. LP activity was determined initially by looking upward and active retraction of upper eyelid with head fixed. Then, dual channel inputs from upper eyelid and masseter muscle was recorded during tooth occlusion motivated by isometric masseter muscle contraction without jaw and face moving. The EMG recorded from upper eyelid when the subjects retracted eyelid with head fixed exhibited the same pattern as that collected during tooth occlusion, but the pattern was completely different from EMG of active eye closure. This reflects tooth occlusion evoked LP activity. Then, simultaneous co-firing of the LP and masseter muscle was recorded simultaneously during tooth occlusion without jaw movement. Finally, the aforementioned co-firing was recorded when the subjects conducted rhythmic occlusion and synchronous EMG from both muscles was acquired. In conclusions, humans may also have an intrinsic masticatory oculomotor circuit and release hypothesis may apply, at least, to some cases of MGS.