Efficient Silver(I)-Containing I-Motif DNA Hybrid Catalyst for Enantioselective Diels-Alder Reactions.

The inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag+-C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag+)/Cu2+) could catalyze Diels-Alder reactions with full conversions and up to 95 % enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag+ is proved to replace the protons in hemiprotonated cytosine-cytosine (C : C+) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag+)/Cu2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu2+. Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively.

Cyclic Dinucleotide-Based Enantioselective Fluorination in Water.

The diverse structures of DNA serve as potent chiral scaffolds for DNA-based asymmetric catalysis, yet in most cases tens to hundreds of nucleotides in DNA hybrid catalysts hinder the deep insight into their structure-activity relationship. Owing to the structural simplicity and design flexibility of nucleotides, nucleotide-based catalysts have been emerging as a promising way to obtain fine structural information and understand the catalytic mechanisms. Herein, we found that a cyclic dinucleotide of cyclic di-AMP (c-di-AMP) and 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO3)2) are assembled to a c-di-AMP-based catalyst (c-di-AMP/Cu(phen)(NO3)2), which could fast achieve enantioselective fluorination in water with 90-99% yields and up to 90% enantiomeric excess (ee). The host-guest interaction between c-di-AMP and Cu(phen)(NO3)2 has been proposed mainly in a supramolecular interaction mode as evidenced by spectroscopic techniques of ultraviolet-visible, fluorescence, circular dichroism, and nuclear magnetic resonance. Cu(phen)(NO3)2 tightly binds to c-di-AMP with a binding constant of 1.7 ± 0.3 × 105 M-1, and the assembly of c-di-AMP/Cu(phen)(NO3)2 shows a modest rate enhancement to carbon-fluorine bond formations as supported by kinetic studies.

Dual Stimuli-Responsive Supramolecular Self-Assemblies Based on the Host-Guest Interaction between ß-Cyclodextrin and Azobenzene for Cellular Drug Release.

Health has always been a hot topic of concern, whereas cancer is one of the largest security risks to human health. Although the existing drug delivery systems (DDSs) have been extensively reported and commercially applied, there are still some issues that have yet to be well-resolved, including the toxicity, side-effects, and targeted therapy efficiency of drugs. Consequently, it is still necessary to develop a novel, highly efficient, controlled and targeted DDS for cancer therapy. For this, a supramolecular polymer, ß-CD-g-PDMAEMA@Azo-PCL, was designed and developed through the host-guest inclusion complexation interactions between a host polymer, ß-cyclodextrin-graft-poly(2-(dimethylamino)ethyl methacrylate) (ß-CD-g-PDMAEMA), and a guest polymer, azobenzene modified poly(ε-caprolactone) (Azo-PCL), and was characterized by various analysis techniques. The supramolecular assembly was examined in various pH environments and/or under UV-vis irradiation, showing the formation of supramolecular assemblies from regular spherical shapes to irregular aggregates with various hydrodynamic diameters. The 2D NOESY NMR studies showed the formation of inclusion complexation between Azo-PCL and ß-CD-g-PDMAEMA and between ß-CD and the side groups of PDMAEMA. The supramolecular assemblies could encapsulate doxorubicin to form spherical core-shell drug-carrying micelles with an entrapment efficiency of 66.1%. The effects of external environment stimuli on the in vitro drug release were investigated, showing light- and pH-modulated drug release properties. The cytotoxicity assessment indicated that the blank supramolecular micelles were nontoxic, whereas the drug-loaded micelles exhibited comparable or even superior anticancer activity to the anticancer activity of free DOX and inhibition of cancer cell proliferation. Therefore, the developed supramolecular assemblies can potentially be used as drug-controlled release carriers.

Preparation and vapor-sensitive properties of hydroxyl-terminated polybutadiene polyurethane conductive polymer nanocomposites based on polyaniline-coated multiwalled carbon nanotubes.

Polyaniline-coated multi-walled carbon nanotube (MWCNT) conductive polymer precursors (MWCNTs@PANI) were prepared by an in situ microemulsion oxidation polymerization of aniline in the case of MWCNTs, and then hydroxyl-terminated polybutadiene polyurethane conductive polymer nanocomposites based on MWCNTs@PANI (MWCNTs@PANI/HTPB PUs) were prepared through an in situ stepwise polymerization of HTPB and diisocyanates. The chemical structure was characterized by Fourier transform infrared spectroscopy (FTIR), Raman, x-ray diffraction, x-ray photoelectron spectroscopy and thermogravimetric analysis. The morphologies and dispersion behavior were examined by scanning electron microscopy, transmission electron microscopy and UV-vis transmittance. The MWCNTs@PANI/HTPB PUs nanocomposites were fabricated into film sensors for detection of volatile organic compound vapors, and displayed an evident response to trichloromethane vapor (CHCl3). The effect of MWCNTs on the conductivity and the responsivity to trichloromethane of conductive polymer nanocomposite films were studied, finding that the conductive composite films have fast and strong response, good repeatability and recoverability, and long-term stability. Consequently, they can be potentially applied for supervision and detection of interior and outdoor environmental gases or vapors.

Highly Efficient Cyclic Dinucleotide Based Artificial Metalloribozymes for Enantioselective Friedel-Crafts Reactions in Water.

The diverse secondary structures of nucleic acids are emerging as attractive chiral scaffolds to construct artificial metalloenzymes (ArMs) for enantioselective catalysis. DNA-based ArMs containing duplex and G-quadruplex scaffolds have been widely investigated, yet RNA-based ArMs are scarce. Here we report that a cyclic dinucleotide of c-di-AMP and Cu2+ ions assemble into an artificial metalloribozyme (c-di-AMP⋅Cu2+ ) that enables catalysis of enantioselective Friedel-Crafts reactions in aqueous media with high reactivity and excellent enantioselectivity of up to 97 % ee. The assembly of c-di-AMP⋅Cu2+ gives rise to a 20-fold rate acceleration compared to Cu2+ ions. Based on various biophysical techniques and density function theory (DFT) calculations, a fine coordination structure of c-di-AMP⋅Cu2+ metalloribozyme is suggested in which two c-di-AMP form a dimer scaffold and the Cu2+ ion is located in the center of an adenine-adenine plane through binding to two N7 nitrogen atoms and one phosphate oxygen atom.

Preparation, film fabrication and gas-sensitive responsive properties of MWCNTs@PS-b-HTPB5-b-PS conductive polymer nanocomposites.

Novel nanocomposites consisting of polystyrene-block-polybutadienyl polyhexamethylene dicarbamate-block-polystyrene (PS-b-HTPB5-b-PS) and multiwalled carbon nanotubes (MWCNTs) were designed and prepared via noncovalent interactions. Scanning electron microscopy and transmission electron microscopy observations showed that segregated networks of MWCNTs were formed due to the cladding of PS-b-HTPB5-b-PS, presenting a parallel-arranged topology of the MWCNTs in a continuous PS-b-HTPB5-b-PS phase, which improved the dispersibility of the MWCNTs. The nanocomposites were fabricated into vapor sensing elements to detect CH2Cl2 vapor in the environment, exhibiting excellent responsive sensitivity, reproducibility and a low limit of detection (LOD) of 1 ppm when exposed to CH2Cl2 vapor. The chain extension of HTPB overcame the fragility and improved the tenacity of the thin films, and the responsivity was optimized by adjusting the content of the MWCNTs and the length of the PS chains. The newly developed conductive composites can be applied as a promising vapor sensor to accurately monitor CH2Cl2 vapor in the environment.

Novel electrochemical sensors from poly[N-(ferrocenyl formacyl) pyrrole]@multi-walled carbon nanotubes nanocomposites for simultaneous determination of ascorbic acid, dopamine and uric acid.

Novel multi-walled carbon nanotubes coated with poly[N-(ferrocenyl formacyl) pyrrole] (MWCNTs@PFFP) nanocomposites were prepared through the in situ oxidation polymerization reaction of N-(ferrocenyl formacyl) pyrrole in the presence of MWCNTs. The MWCNTs@PFFP nanocomposites were characterized by FT-IR, Raman, TGA, XRD, XPS, SEM and TEM techniques. The MWCNTs@PFFP nanocomposites were fabricated into novel electrochemical sensors for simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The electrochemical behavior of the MWCNTs@PFFP/GCE sensors was examined, and the parameters that influence electrochemical signals were optimized. The experimental results showed that the fabricated modified electrode sensors exhibited good sensitivity, selectivity, specificity, repeatability and a long lifetime, remaining the initial current of at least 92.5% after 15 days storage in air. The sensors possessed a linear response concentration range over 200-400 µM for AA, 2-16 µM for both DA and UA, and a limit of detection as low as 40.0, 1.1 and 7.3 × 10-1 µM for AA, DA and UA, respectively. They are expected to be used as a potential tool for the simultaneous detection of DA, AA and UA in the human body.

Construction of Crowning ß-cyclodextrin with Temperature Response and Efficient Properties of Host-Guest Inclusion.

Promoting a drug inclusion proportion in hydrophobic cavity of ß-cyclodextrin using simple methods is a highly ambitious task. Herein, we report the crowning ß-cyclodextrins formed by intramolecular hydrogen bonding interaction, which has greatly prolonged the cavity depth of ß-cyclodextrin, and therefore further efficiently improved the inclusion proportion to complex drug molecule (vitamin E). Furthermore, the self-assembly behaviors, controllable release, and antioxidant properties of vitamin E embedded into the cavity of crowning ß-cyclodextrins was investigated, and host-guest inclusions exhibited temperature-responsive controlled release, excellent antioxidant activity, and photostability.

3D Graphene Frameworks/Co3 O4 Composites Electrode for High-Performance Supercapacitor and Enzymeless Glucose Detection.

3D graphene frameworks/Co3 O4 composites are produced by the thermal explosion method, in which the generation of Co3 O4 nanoparticles, reduction of graphene oxide, and creation of 3D frameworks are simultaneously completed. The process prevents the agglomeration of Co3 O4 particles effectively, resulting in monodispersed Co3 O4 nanoparticles scattered on the 3D graphene frameworks evenly. The prepared 3D graphene frameworks/Co3 O4 composites used as electrodes for supercapacitor display a definite improvement on electrochemical performance with high specific capacitance (≈1765 F g-1 at a current density of 1 A g-1 ), good rate performance (≈1266 F g-1 at a current density of 20 A g-1 ), and excellent stability (≈93% maintenance of specific capacitance at a constant current density of 10 A g-1 after 5000 cycles). In addition, the composites are also employed as nonenzymatic sensors for the electrochemical detection of glucose, which exhibit high sensitivity (122.16 µA mM -1  cm-2 ) and noteworthy lower detection limit (157 × 10-9 M, S/N = 3). Therefore, the authors expect that the 3D graphene frameworks/Co3 O4 composites described here would possess potential applications as the electrode materials in supercapacitors and nonenzymatic detection of glucose.

Dual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) copolymer micromicelles: surface RAFT synthesis, self-assembly and drug release applications.

BACKGROUND: Stimuli-responsive polymer materials are a new kind of intelligent materials based on the concept of bionics, which exhibits more significant changes in physicochemical properties upon triggered by tiny environment stimuli, hence providing a good carrier platform for antitumor drug delivery. RESULTS: Dual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) block copolymers (Fe3O4-g-PAA-b-PMAEFC) were engineered and synthesized through a two-step sequential reversible addition-fragmentation chain transfer polymerization route. The characterization was performed by FTIR, 1H NMR, SEC, XRD and TGA techniques. The self-assembly behavior in aqueous solution upon triggered by pH, magnetic and redox stimuli was investigated via zeta potentials, vibration sample magnetometer, cyclic voltammetry, fluorescent spectrometry, dynamic light scattering, XPS, TEM and SEM measurements. The experimental results indicated that the Fe3O4-g-PAA-b-PMAEFC copolymer materials could spontaneously assemble into hybrid magnetic copolymer micromicelles with core-shell structure, and exhibited superparamagnetism, redox and pH stimuli-responsive features. The hybrid copolymer micromicelles were stable and nontoxic, and could entrap hydrophobic anticancer drug, which was in turn swiftly and effectively delivered from the drug-loaded micromicelles at special microenvironments such as acidic pH and high reactive oxygen species. CONCLUSION: This class of stimuli-responsive copolymer materials is expected to find wide applications in medical science and biology, etc., especially in drug delivery system.

Thermosensitive mPEG-b-PA-g-PNIPAM comb block copolymer micelles: effect of hydrophilic chain length and camptothecin release behavior.

PURPOSE: Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. METHODS: The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV-vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. RESULTS: The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96-27.64 mg L(-1). The micelles were narrow-size-distribution, with hydrodynamic diameters about 128-193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. CONCLUSIONS: The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

A Bioinspired Skin UV Filter with Broadband UV Protection, Photostability, and Resistance to Oxidative Damage.

In recent years, sunscreens' adverse impacts on the environment and biology have gained wide attention. The improvement of sunscreen safety has become one of the major priorities in skin photoprotection research. It is an effective strategy to develop bionic photoprotective materials by simulating the photoprotective mechanism existing in nature. Inspired by the photoprotective mechanisms of skin and plant leaves, the bionic photoprotective material CS-SA-PDA nanosheet was developed using the free radical grafting method and Michael addition, with natural melanin analogue polydopamine (PDA) nanoparticles and plant sunscreen molecular sinapic acid (SA) as sun protection factors and natural polymer chitosan (CS) as the connecting arm. The results show that CS-SA-PDA can effectively shield UVB and UVA due to the possible synergistic effect between PDA and SA. The introduction of polymer CS significantly improved the photostability of SA and reduced the skin permeability of PDA nanoparticles. The CS-SA-PDA nanosheet can also effectively scavenge photoinduced free radicals. Furthermore, in vivo toxicity and anti-UV evaluations confirm that CS-SA-PDA has no skin irritation and is excellent against skin photodamage, which makes it an ideal skin photoprotective material.

pH-sensitive carbon nanotubes graft polymethylacrylic acid self-assembly nanoplatforms for cellular drug release.

pH-Sensitive carbon nanotubes graft polymethylacrylic acid hybrids (CNTs-g-PMAA) were prepared through a three-step process, and self-assembled into core-shell micelle nanoparticles. The chemical structure of the hybrids were characterized by FTIR, 1H NMR and TGA. The critical micelle concentration (CMC) was measured by surface tension, and the value hinged on the Mn values or chain lengths of PMAA segments. The UV-vis transmittance, dynamical light scattering (DLS), and zeta potential measurements indicated that the hybrid self-assembly exhibited pH-sensentive responsiveness. The self-assembly was used to load an anticancer drug, paclitaxel (PTX), with an encapsulation efficiency of 77%. The PTX-loaded hybrid drug preparations were applied for cancer-cellular drug release, finding that the release rate was dependent on pH environments, and faster in acidic media of pH < 6.8 than in pH 7.4. MTT and hemolysis assays manifested that the blank hybrid drug carriers were nontoxic and safe, whereas the PTX-loaded drug preparations possessed comparable and even higher anticancer activity in comparison with free PTX. Consequently, the developed hybrid drug nanocarriers can be used for cancer therapy as a promising candidate.

Rational design of dual-functional surfaces on polypropylene with antifouling and antibacterial performances via a micropatterning strategy.

The hydrophobicity and inertness of the polypropylene (PP) material surface usually lead to serious biofouling and bacterial infections, which hamper its potential application as a biomedical polymer. Many strategies have been developed to improve its antifouling or antibacterial properties, yet designing a surface to achieve both antifouling and antibacterial performances simultaneously remains a challenge. Herein, we construct a dual-function micropatterned PP surface with antifouling and antibacterial properties through plasma activation, photomask technology and ultraviolet light-induced graft polymerization. Based on the antifouling agent poly(2-methacryloyloxyethyl phosphate choline) (PMPC) and the antibacterial agent quaternized poly(N,N-dimethylamino)ethyl methacrylate (QPDMAEMA), two different micropatterning structures have been successfully prepared: PP-PMPC-QPDMAEMA in which QPDMAEMA is the micropattern and PMPC is the coating polymer, and PP-QPDMAEMA-PMPC in which PMPC is the micropattern and QPDMAEMA is the coating polymer. The composition, elemental distribution and surface morphology of PP-PMPC-QPDMAEMA and PP-QPDMAEMA-PMPC have been thoroughly characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. Compared with pristine PP, the two types of micropatterned PP films exhibit good surface hydrophilicity as characterized by water contact angle measurements. The results of anti-protein adsorption, platelet adhesion and antibacterial evaluation showed that PP-PMPC-QPDMAEMA and PP-QPDMAEMA-PMPC had good anti-protein adsorption properties, especially for lysozyme (Lyz). They can effectively prevent platelet adhesion, and the anti-platelet adhesion performance of PP-QPDMAEMA-PMPC is slightly better than that of the PP-PMPC-QPDMAEMA sample. The sterilization rate of S. aureus and E. coli is as high as 95% for the two types of micropatterned PP films. Due to the rational design of micropatterns on the PP surface, the two classes of dual-functional PP materials realize both the resistance of protein and platelet adhesion, and the killing of bacteria at the same time. We anticipate that this work could provide a design strategy for the construction of multifunctional biomedical polymer materials.

Construction of multifunctional micro-patterned PALNMA/PDADMAC/PEGDA hydrogel and intelligently responsive antibacterial coating HA/BBR on Mg alloy surface for orthopedic application.

In recent years, magnesium alloys (MgA) have been reckoned as the most promising material of biomedical importance on account of its excellent degradable properties and mechanical properties mimicking natural bone tissues. However, MgA are prone to rapid corrosion under physiological conditions, causing toxicity around the neighboring tissues. In addition, they are susceptible to bacterial colonization, a detrimental factor for medical causes. In this study, antibacterial material coated hydrogel-based micro-patterns were developed on MgA to achieve long-term antibacterial, antifouling, osteogenic, and cell-compatible properties. First, the Mg(OH)2 nanosheet coating was prepared on the surface of MgA as a physical barrier to prevent the corrosion of MgA. Then the hydrogel micropatterns of poly(alendronate sodium methacrylate)/poly(dimethyldiallylammonium chloride)/poly(ethylene glycol) diacrylate (PALNMA/PDADMAC/PEGDA) of different sizes were constructed on the surface of the Mg(OH)2 coating using the photomask method. Finally, an intelligently responsive antibacterial material hyaluronic acid/berberine (HA/BBR) was coated on MgA-Mg(OH)2-PALNMA/PDADMAC/PEGDA patterns via layer-by-layer self-assembly. The excellent antifouling performance of the samples is attributed to the topological structure of the pattern. Interestingly, as the pattern size of PALNMA/PDADMAC/PEGDA decreases, the antibacterial, antifouling, and cell compatibility properties of the samples gradually improve. UV-Vis spectra and bacterial plate count indicate that HA/BBR coating provide a pH and hyaluronidase (HAase) dual-responsive surface to kill the attached bacteria quickly. Finally, the in vitro experiments demonstrate excellent blood compatibility, cell compatibility and osteogenic properties of the modified MgA samples. Therefore, the intelligent multifunctional assembly of MgA presented here has a promising future in the field of metal implant materials.

Functional composite hydrogels entrapping polydopamine hollow nanoparticles for highly efficient resistance of skin penetration and photoprotection.

Living organisms tend to evolve various naturally photoprotective mechanisms to avoid photodamage. Among them, polydopamine (PDA) is an effective sunscreen, a mimic of melanin, which is the main functional component of the photoprotective system of human skin. However, the concerns of its dark color, skin penetration and photoprotective efficiency remain yet to be solved. Herein, we have constructed melanin-inspired nanocomposite hydrogels (CS-PDAh-GP-HA) for photoprotection, in which PDA was prepared as hollow nanoparticles (PDAh NPs) and entrapped in a physically cross-linked hydrogel (CS-GP-HA) formed by chitosan (CS) and hyaluronic acid (HA) using ß-glycerophosphate (ß-GP) as a modulator. The CS-PDAh-GP-HA hydrogels exhibit a shear-thinning flow behavior with an elastic modulus of 300 Pa with the gel-sol transition temperature maintained at about 37 °C simply by adjusting the ß-GP content in the hydrogels. The CS-PDAh-GP-HA hydrogels also possess excellent resistance toward skin penetration. The photoprotective performances of CS-PDAh-GP-HA hydrogels were evaluated by the determination of sun protection factor (SPF) and in vitro UVA protection efficacy (UVAPE) along with UV-Vis spectroscopy. Compared with the TiO2 nanoparticles in CS-GP-HA hydrogel, the CS-PDAh-GP-HA hydrogels show stronger shielding ability in both UVA and UVB regions. When protected by the CS-PDAh-GP-HA hydrogels, the cell viability of NIH-3T3 fibroblasts increases to 96% while it was only 14% in the case of non-protecting group. These results suggest that the CS-PDAh-GP-HA hydrogels could efficiently shield the UV irradiation and protect the skin from photodamage. This work introduces PDA-based nanocomposite hydrogels with safe, biocompatible and photoprotective properties, and provides a melanin-mimicking photoprotection system for the application in sunscreens.

Temperature and Photo Dual-Stimuli Responsive Block Copolymer Self-Assembly Micelles for Cellular Controlled Drug Release.

To well adapt to the complicated physiological environments, it is necessary to engineer dual- and/or multi-stimuli responsive drug carriers for more effective drug release. For this, a novel temperature responsive lateral chain photosensitive block copolymer, poly[(N-isopropylacrylamide-co-N,N-dimethylacrylamide) -block-propyleneacylalkyl-4-azobenzoate] (P(NIPAM-co-DMAA)-b-PAzoHPA), is synthesized by atom transfer radical polymerization. The structure is characterized by 1 H nuclear magnetic resonance spectrometry and laser light scattering gel chromatography system. The self-assembly behavior, morphology, and sizes of micelles are investigated by fluorescence spectroscopy, transmission electron microscope, and laser particle analyzer. Dual responsiveness to light and temperature is explored by ultraviolet-visible absorption spectroscopy. The results show that the copolymer micelles take on apparent light and temperature dual responsiveness, and its lower critical solution temperature (LCST) is above 37 °C, and changes with the trans-/cis- isomerization of azobenzene structure under UV irradiation. The blank copolymers are nontoxic, whereas the paclitaxel (PTX)-loaded counterparts possessed comparable anticancer activities to free PTX, with entrapment efficiency of 83.7%. The PTX release from the PTX-loaded micelles can be mediated by changing temperature and/or light stimuli. The developed block copolymers can potentially be used for cancer therapy as drug controlled release carriers.

Injectable Enzyme-Based Hydrogel Matrix with Precisely Oxidative Stress Defense for Promoting Dermal Repair of Burn Wound.

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol-Fe3+ coordination hydrogel (MICH) matrix, is engineered to promote burn-wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of "Fe-superoxide dismutases," small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn-wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress.

Rational Design of PMPC/PDMC/PEGDA Hydrogel Micropatterns onto Polylactic Acid with Enhanced Biological Activity.

Polylactic acid (PLA) is one of the biodegradable materials that has been used in the areas of surgical healing lines, cancer treatment, and wound healing. However, the application of PLA is still rather limited due to its high hydrophobicity and poor antibacterial activity. In order to enhance the antifouling and antibacterial performances of PLA, here we modified the surface of PLA with various sizes of hydrogel micropatterns in negative or positive mode using plasma treatment, the photomask technique, and UV-graft polymerization. The hydrogel micropatterns consist of poly(ethylene glycol) diacrylate (PEGDA), poly(2-methacryloyloxyethylphosphorylcholine) (PMPC), and poly(methacryloyloxyethyltrimethylammonium chloride) (PDMC). Compared to PLA, the patterned PLA (PLA-PMPC/PDMC/PEGDA) shows obviously enhanced antifouling and antibacterial activities. For PLA-PMPC/PDMC/PEGDA with either positive or negative micropatterns, the antifouling and antibacterial properties are gradually increasing with decreasing the size of micropatterns. Compared with PLA-PMPC/PDMC/PEGDA bearing positive and negative micropatterns in the same size, the PLA-PMPC/PDMC/PEGDA with negative micropatterns exhibits slightly better biological activity and the PLA-PMPC/PDMC/PEGDA with 3 µm negative hydrogel micropatterns shows the best hydrophilicity, antifouling, and antibacterial properties. Combining the in vitro hemolysis assay, cytotoxicity, water absorption test, and degradation test results, it is suggested that the fabrication of hydrogel micropatterns onto the PLA surface could significantly improve biological activities of PLA. We expect that this work would provide a new strategy to potentially develop PLA as a promising wound dressing.

Elastic, Persistently Moisture-Retentive, and Wearable Biomimetic Film Inspired by Fetal Scarless Repair for Promoting Skin Wound Healing.

An efficient and available material for promoting skin regeneration is of great importance for public health, but it remains an elusive goal. Inspired by fetal scarless wound healing, we develop a wearable biomimetic film (WBMF) composed of hyaluronan (HA), vitamin E (VE), dopamine (DA), and ß-cyclodextrin (ß-CD) that mimics the fetal context (FC) and fetal extracellular matrix (ECM) around the wound bed for dermal regeneration. First, the WBMF creates the FC of sterility, hypoxia, persistent moisture, and no secondary insults for wounds as the result of its seamless adhesion to the skin, optimum stress-stretch and high-cycle fatigue resistance matching the anisotropic tension of the skin, and water-triggered self-healing behavior. Thus, the WBMF modulates the early wound situation to minimize inflammatory response. In the meantime, the WBMF mimics the critical biological function of fetal ECM, inducing fibroblast migration, suppressing the overexpression of transforming growth factor ß1, and mediating collagen synthesis, distribution, and reestablishment. As a result, the WBMF accelerates wound healing and gains a normal dermal collagen architecture, thereby restoring scarless appearance. Overall, the WBMF provides a new paradigm for promoting skin wound healing and may find broad utility for the field of regenerative medicine.