Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

A review on microbial synthesis of lactate-containing polyesters.

Degradable polylactic acids (PLA) have been widely used in agriculture, textile, medicine and degradable plastics industry, and can completely replace petroleum-based plastics in the future. At present, polylactic acid was chemically synthesized by ring-opening polymerisation or the direct polycondensation of lactic acid, which inevitably leads to chemical and heavy metal catalyst pollution. The current research focus has gradually shifted to the development of recombinant industrial strains for the efficiently production of lactate-containing polyesters from renewable resources. This review summarizes various explorations of metabolic pathway optimization and production cost control in the industrialization of lactate-containing polyesters bio-production. In particular, the effects of key enzymes, including CoA transferase, polyhydroxyalkanoate synthase, and their mutants, culture conditions, low-cost carbon sources, and recombinant strains on the yield and composition of lactate-containing polyesters are summarized and discussed. Future prospects and challenges for the industrialization of lactate-containing polyesters are also pointed out.

Magnetic mesoporous silica nanoparticles-aided dual MR/NIRF imaging to identify macrophage enrichment in atherosclerotic plaques.

Active foamy macrophage enrichment drives atherosclerotic plaque initiation and evolution, and is the prominent target for precisely identifying vulnerable plaque. Precise imaging of high-risk plaque allows promotion of treatment and prevention of vascular pathema. However, current iron oxide (IO) nanoparticles-based magnetic resonance (MR) imaging of plaque is often limited by insufficient perfusion and nonspecific accumulation of peri-aortic lymph nodes. Besides that, intrinsic defects of MR also impede its use for accurately identifying plaque details. Herein, by conjugating with PP1 peptide, a novel magnetic mesoporous silica nanoparticle (PIMI) loaded with near-infrared fluorescence (NIRF) dye (IR820) was fabricated to specifically target and quantify macrophage enrichment of atherosclerotic plaque in ApoE-/- mice using dual MR/NIRF imaging. Biocompatibility experiments ulteriorly confirmed the high safety of PIMI nanoparticles in vivo, which lays the foundation of next-generation contrast agent for recognizing macrophage-rich plaque in the near future.

Softening and Shape Morphing of Stiff Tough Hydrogels by Localized Unlocking of the Trivalent Ionically Cross-Linked Centers.

The mechanical properties (e.g., stiffness, stretchability) of prefabricated hydrogels are of pivotal importance for diverse applications in tissue engineering, soft robotics, and medicine. This study reports a feasible method to fabricate ultrasoft and highly stretchable structures from stiff and tough hydrogels of low stretchability and the application of these switchable hydrogels in programmable shape-morphing systems. Stiff and tough hydrogel structures are first fabricated by the mechanical strengthening of Ca2+ -alginate/polyacrylamide tough hydrogels by addition of Fe3+ ions, which introduces Fe3+ ionically cross-linked centers into the Ca2+ divalent cross-linked hydrogel, forming an additional and much less flexible trivalent ionically cross-linked network. The resulting stiff and tough hydrogels are exposed to an L-ascorbic acid (vitamin C, VC) solution to rapidly reduce Fe3+ to Fe2+ . As a result, flexible divalent ionically cross-linked networks are formed, leading to swift softening of the stiff and tough hydrogels. Moreover, localized stiffness variation of the tough hydrogels can be realized by precise patterning of the VC solution. To validate this concept, sequential steps of VC patterning are carried out for local tuning of the stiffness of the hydrogels. With this strategy, localized softening, unfolding, and sequential folding of the tough hydrogels into complex 3D structures is demonstrated.

A human cell panel for evaluating safe application of nano-ZrO2/polymer composite in water remediation.

Nanomaterials, such as ZrO2 nanoparticles (ZrO2 NPs), are very effective in water remediation. However, the safety issues related to nanoparticle release and toxicity to humans remain to be resolved. Here we evaluated the cytotoxicity of ZrO2 NPs and their adducts with pollutants using a human cell panel containing stomach, intestine, liver and kidney cells. We found that different pollutants or ZrO2NP/pollutant adducts targeted cells from different organs, suggesting the necessity of a cell panel to model oral exposures. The cooperation of ZrO2 NPs and pollutants was quite complex, consisting of synergistic, antagonistic, or additive effects. For example, ZrO2 NPs enhanced the cytotoxicity of Pb2+ in GES-1 cells and of Pb2+, Cd2+ in FHC cells, while alleviating the toxicity of Pb2+ and As (III) in HepG2 and Hek293 cells. Our results also indicated that even concentrations of pollutants that meet the national standard, the ZrO2 NPs concentration should be kept below 17 µg/mL to avoid ZrO2 NP/pollutant adduct synergistic toxicity.

Eudragit S100 coated nanodiamond-based nanoparticles as an oral chemo-photothermal delivery system for local treatment of colon cancer.

Oral colonic nano-drug delivery system has received more and more attention in the treatment of colon cancer due to local precision treatment and reduction of drug system distribution. However, the complex and harsh gastrointestinal environment and the retention of nanoparticles in the colon limit its development. To this end, we designed Eudragit S100 (ES) coated nanoparticles (ES@PND-PEG-TPP/DOX). Polydopamine coated nanodiamond (PND) was modified with amino-functionalized polyethylene glycol (NH2-PEG-NH2) and triphenylphosphine (TPP) successively. Due to the high specific surface area of PND, it can efficiently load the model drug doxorubicin hydrochloride (DOX). In addition, PND also has high photothermal conversion efficiency, generating heat to kill cancer cells under near infrared (NIR) laser, realizing the combination of chemotherapy and photothermal therapy (CT-PTT). TPP modification enhanced nanoparticle uptake by colon cancer cells and prolonged preparations retention time at the colon. ES shell protected the drug from being destroyed and prevented the nanoparticles from sticking to the small intestine. Ex vitro fluorescence imaging showed that TPP modification can enhance the residence time of nanoparticles in the colon. In vivo pharmacodynamics demonstrated that CT-PTT group has the greatest inhibitory effect on tumor growth, which means that the nanocarrier has potential clinical value in the in-situ treatment of colon cancer.

Biocompatibility FeOOH QD@ATP-BODIPY nanocomposite for glutathione detection and intracellular imaging.

Monitoring of glutathione has attracted considerable attention owing to its biological and clinical significance. An eco-friendly, economic, simple, biocompatible probe with excellent sensitivity and selectivity is very important. Herein, FeOOH QD@ATP-BODIPY nanocomposite was fabricated from one-step synthesized FeOOH quantum dots (FeOOH QD) and commercial boron-dipyrromethene-conjugated adenosine 5'-triphosphate (ATP-BODIPY) for glutathione (GSH) sensing in solutions and living cells. Three fascinate merits of FeOOH QD were confirmed: (a) as fluorescence quencher for ATP-BODIPY, (b) as selective recognizer of GSH and (c) with carrier effects and membrane permeability. The construction and response mechanism of the nanocomposite was based on the competitive coordination chemistry and redox reaction of FeOOH QD between GSH and phosphate group of ATP-BODIPY. Under the optimal conditions, the detection limit for GSH was as low as 68.8 nM. Excellent linear range of 0.2-400 µM was obtained. Furthermore, the chemical response of the nanocomposite exhibits high selectivity toward GSH over other electrolytes and biomolecules. It was successfully applied for GSH determination in human serum samples. The MTT assay exhibited FeOOH QD@ATP-BODIPY nanocomposite own good biocompatibility. FeOOH QD@ATP-BODIPY respond to GSH in living cells in situ was also proved via fluorescence imaging. These suggested that the FeOOH QD@ATP-BODIPY nanocomposite had potential application in biological and clinical applications.

Conformational Properties of Polymers at Droplet Interfaces as Model Systems for Disordered Proteins.

Polymer models serve as useful tools for studying the formation and physical properties of biomolecular condensates. In recent years, the interface dividing the dense and dilute phases of condensates has been discovered to be closely related to their functionality, but the conformational preferences of the constituent proteins remain unclear. To elucidate this, we perform molecular simulations of a droplet formed by phase separation of homopolymers as a surrogate model for the prion-like low-complexity domains. By systematically analyzing the polymer conformations at different locations in the droplet, we find that the chains become compact at the droplet interface compared with the droplet interior. Further, segmental analysis revealed that the end sections of the chains are enriched at the interface to maximize conformational entropy and are more expanded than the middle sections of the chains. We find that the majority of chain segments lie tangential to the droplet surface, and only the chain ends tend to align perpendicular to the interface. These trends also hold for the natural proteins FUS LC and LAF-1 RGG, which exhibit more compact chain conformations at the interface compared to the droplet interior. Our findings provide important insights into the interfacial properties of biomolecular condensates and highlight the value of using simple polymer physics models to understand the underlying mechanisms.

Fabrication of highly porous, functional cellulose-based microspheres for potential enzyme carriers.

Here, we present highly porous, cellulose-based microspheres using (2,2,6,6-tetramethylpiperidine-1-oxyl) TEMPO-oxidized cellulose fibers (TOCFs) as starting materials. The TOCFs were first dissolved in a NaOH/urea solvent and transformed into microspheres via an emulsification method. The carboxyl groups on the surface of TOCFs were successfully carried on the cellulose-based microspheres, which provides them numerous reacting or binding sites, allowing them to be easily functionalized or immobilized with biomolecules for multi-functional applications. Furthermore, the introduction of magnetic nanoparticles awards these microspheres magnetic properties, allowing them to be attracted by a magnetic field. As a proof of concept, we demonstrate the application of using these carboxylate cellulose-based microspheres for enzyme immobilization. The cellulose-based microspheres can successfully create stable covalent bonds with enzymes after the activation of carboxyl groups. The enhanced pH tolerance, thermal stability, convenient recovery, and reusability position the emulsified microspheres as promising carriers for enzyme immobilization.

Identification of Phthalates from Artificial Products in Chinese Kindergarten Classrooms and the Implications for Preschool Children's Exposure Assessments.

Phthalates are typical chemical pollutants in kindergarten classrooms since numerous artificial products (e.g., polyvinyl chloride (PVC) floorings, soft polymers and plastic toys) that might contain phthalates are widely distributed in kindergarten classrooms. Although Chinese preschool children spend a considerable amount of their waking hours (>8 h/day) in kindergartens, phthalate exposure in such indoor environment has not been given much attention. In this study, the mass fractions of six phthalates in twenty-six artificial products (fifteen flat decoration materials and eleven plastic toys) commonly found in Chinese kindergarten classrooms were measured. Di-2-ethylhexyl phthalate (DEHP) was the most predominant compound in all materials. The emission characteristics of the DEHP from these materials were further investigated. The measured emission characteristics were used for predicting multi-phase DEHP concentrations in kindergarten classrooms by applying a mass transfer model. The modeled concentrations were comparable with those measured in the real environment, indicating that these products might be the major sources of DEHP in Chinese kindergarten classrooms. Preschool children's exposure to DEHP was found to be 0.42 µg/kg/day in kindergartens under baseline conditions, accounting for 18% of the total exposure to DEHP in Chinese indoor environments.

Legumain protease-sheddable PEGylated, tuftsin-modified nanoparticles for selective targeting to tumour-associated macrophages.

Tumour-associated macrophages (TAMs) represent an attractive cell target for anticancer therapy. However, selective and efficient targeting of TAMs remains difficult. Here, we constructed a novel dually functionalised nanoparticle platform (s-Tpep-NPs) by surface co-modification of nanoparticles (NPs) with tuftsin (Tpep) and legumain protease-sheddable polyethylene glycol 5k (PEG5k) to achieve selective targeted delivery to TAMs. The fluorescence resonance energy transfer experiment and in vitro cellular uptake assay confirmed that s-Tpep-NPs can responsively shed PEG5k and transform into active Tpep-NPs upon the cleavage of legumain that is overexpressed on TAM surfaces, which then promotes TAM phagocytosis through Fc receptor-mediated pathways. Owing to the shielding effect by legumain-sheddable PEG5k, s-Tpep-NPs can effectively decrease the Tpep-induced non-specific accumulation in mononuclear phagocyte system (MPS) organs during systemic circulation. Moreover, s-Tpep-NPs can significantly enhance the tumoural accumulation and improve the specificity and efficiency of targeting to TAMs, as compared with both controls of Tpep-NPs and non-sheddable ns-Tpep-NPs. Overall, this study provides a robust nanoplatform with a novel avenue for improved selectivity of targeted delivery to TAMs.

Fabrication, GSH-responsive drug release, and anticancer properties of thioctic acid-based intelligent hydrogels.

Injectable hydrogels are potential local drug delivery systems since they contain plenty of water and soft like biological tissues. Such hydrogels could be injected directly into the tumor site where the drug is released under the tumor microenvironment. However, drug loaded hydrogels for cancer treatment based on lipoic acid (natural small molecule) have not been exploited. Here, a novel poly(lipoic acid)-poly(ethylene glycol) (PEG-PTA) hydrogels were prepared through a two-step reaction. The hydrogels contained disulfide bonds, so they could be degraded via the thiol exchange reaction with the abundant GSH in the tumor microenvironment, and subsequently release the drug. The results in vitro and at cellular level showed that the hydrogels were degraded and released the drugs only in the presence of GSH. Therefore, the injectable GSH-responsive hydrogels are promising to be served as an intelligent drug delivery system for cancer treatment.

A nanoparticle-containing polycaprolactone implant for combating post-resection breast cancer recurrence.

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.

Study of POSS on the Properties of Novel Inorganic Dental Composite Resin.

: Various amounts of methacryl polyhedral oligomeric silsesquioxane (POSS) were explored to be incorporated into novel nano SiO2 dental resin composites using light curing method. The scanning electron microscopy (SEM), optical microscopy, fourier transform infrared spectroscopy (FTIR), nanoindentation, nanoscratch and three-point flexure tests were performed. The volumetric shrinkage and mechanical properties such as hardness, elastic modulus, resistance, flexural strength and fracture energy were analyzed. With the additions of POSS, the volume shrinkage decreased and the mechanical properties initially increased. The effects of POSS on these properties were studied to provide a reference for clinically selecting a composite resin with excellent properties.

Nanotunnels within Poly(3,4-ethylenedioxythiophene)-Carbon Nanotube Composite for Highly Sensitive Neural Interfacing.

Neural electrodes are developed for direct communication with neural tissues for theranostics. Although various strategies have been employed to improve performance, creating an intimate electrode-tissue interface with high electrical fidelity remains a great challenge. Here, we report the rational design of a tunnel-like electrode coating comprising poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotubes (CNTs) for highly sensitive neural recording. The coated electrode shows a 50-fold reduction in electrochemical impedance at the biologically relevant frequency of 1 kHz, compared to the bare gold electrode. The incorporation of CNT significantly reinforces the nanotunnel structure and improves coating adhesion by ∼1.5 fold. In vitro primary neuron culture confirms an intimate contact between neurons and the PEDOT-CNT nanotunnel. During acute in vivo nerve recording, the coated electrode enables the capture of high-fidelity neural signals with low susceptibility to electrical noise and reveals the potential for precisely decoding sensory information through mechanical and thermal stimulation. These findings indicate that the PEDOT-CNT nanotunnel composite serves as an active interfacing material for neural electrodes, contributing to neural prosthesis and brain-machine interface.

Case report of primary Sjögren Syndrome with simple trigeminal lesion as initial symptom.

PURPOSE: It will provide a reference for early detection, early diagnosis and early treatment of atypical primary Sjogren syndrome with neurological impairment as the first symptom. METHODS: Case report and Literature review. RESULTS: Here we report a 30-year-old woman diagnosed with trigeminal damage secondary to pSS who presented atypical trigeminal neuralgia of numbness of the right head and face and persistent prickling-like pain not associated with eating, talking or tooth-brushing, and had no "trigger point". The patient further received rheumatoid immune factor tests, ophthalmic examinations, salivary gland emissioncomputed tomography(ECT) and lip biopsy, and found positive antinuclear antibodies (1:320), atypical xerophthalmia, impaired intake and excretion of bilateral salivary glands and degree II of lip biopsy. The patient received methylprednisolone and antiviral therapy, which showed very good outcome. CONCLUSIONS: Clinically primary Sjögren Syndrome (pSS) combined with trigeminal lesion is common, but cases of pSS with trigeminal involvement as initial symptom have rarely been reported, which is easy to misdiagnose. This case suggested that the signs of simple trigeminal lesion, especially those with atypical manifestations, could be the early manifestation of other systemic diseases. Attention should be paid to identification of the pathogeny of the primary disease to achieve early identification, diagnosis and treatment.

Flexible and self-adaptive neural ribbon with three-dimensional electrodes for sciatic nerve recording.

Various peripheral nerve interfaces have been developed in the last decades and transferred into neuroscientific researches or clinical applications. In this study, we present a novel flexible neural ribbon electrode that can achieve self-adaption to nerves in various diameters and have three dimensional (3D) contacts. Impedance spectroscopy of the neural ribbon electrode was carried out to determine its electrochemical characteristics during the recording. The recording capability of the neural ribbon on sciatic nerves with different diameter was demonstrated by successful signal acquisitions.