Bioinspired Microadhesives with Greatly Enhanced Reversible Adhesion Fabricated by Synthesized Silicone Elastomer with Increasing Phenyl Contents.

We present a facile chemical method for fabricating bioinspired microadhesives with significant improved reversible adhesion strength. Four kinds of polysiloxane with gradient varying phenyl contents were synthesized and used to fabricate microadhesives. The chemical structures and mechanical properties, as well as surface properties of the four microadhesives, were confirmed and characterized by ATR-FTIR, DSC, XPS, low-field NMR, tensile tests, and SEM, respectively. The macroadhesion test results revealed that phenyl contents showed remarkable and positive impacts on the macroadhesion performance of microadhesives. The pull-off adhesion strength of microadhesives with 90% phenyl content (0.851 N/cm2) was nearly 300% higher than that of pure PDMS (0.309 N/cm2). The macroadhesion mechanism analysis demonstrates that a larger bulk energy dissipation caused by massive π-π interaction, as well as the hydrophobic interaction and van der Waals forces at the interface synergistically resulted in a significant enhancement of the adhesion performance. Our results demonstrate the remarkable impact of chemical structures on the adhesion of microadhesives, and it is conducive to the further improvement of adhesion properties of bioinspired microadhesives.

Multi-tasking geometric phase element array based self-referenced vortex interferometer for three-dimensional topography.

Interferometry is a basic physical method to record and reconstruct the three-dimensional (3D) topography of a complex object. However, mainstream interferometers using two beams can be unstable in a volatile environment. Here, we present a self-referenced optical vortex interferometer employing multi-tasking geometric phase elements. Compared with conventional devices, the multitasking elements can enable vortex filters while deflecting the interference beams to achieve high mode purity in broadband. We use the proposed system to reconstruct the 3D topography of a sample while determining its surface elevations and depressions accurately and conveniently in one static interference pattern.

Arene Substitution Design for Controlled Conformational Changes of Dibenzocycloocta-1,5-dienes.

We report that an agile eight-membered cycloalkane can be stabilized by fusing a benzene ring on each side, substituted with proper functional groups. The conformational change of dibenzocycloocta-1,5-diene (DBCOD), a rigid-flexible-rigid organic moiety, from its Boat to Chair conformation requires an activation energy of 42 kJ/mol, which is substantially lower than those of existing submolecular shape-changing units. Experimental data corroborated by theoretical calculations demonstrate that intramolecular hydrogen bonding can stabilize Boat, whereas electron repulsive interaction from opposing ester substituents favors Chair. Intramolecular hydrogen bonding formed by 1,10-diamide substitution stabilizes Boat, spiking the temperature at which Boat and Chair can readily interchange from -60 to 60 °C. Concomitantly this intramolecular attraction raises the energy barrier from 42 kJ/mol for unsubstituted DBCOD to 68 kJ/mol for diamide-substituted DBCOD. Remarkably, this value falls within the range of the activation energy of highly efficient enzyme-catalyzed biological reactions. With shape changes once considered only possible with high energy, our work reveals a potential pathway exemplified by a specific submolecular structure to achieve low-energy-driven shape changes for the first time. The intrinsic cycle stability and high-energy output systems that would incur damage under high-energy stimuli could particularly benefit from this new kind of low-energy-driven shape-changing mechanism. This work has laid the basis to construct systems for low-energy-driven stimuli-responsive applications, hitherto a challenge to overcome.

Temperature and pH Responsive Janus Silica Nanoplates Prepared by the Sol-Gel Process and Postmodification.

During the process of emulsifying and hydrolyzing, reactive poly(3-(triethoxysilyl)propyl methacrylate)-b-polystyrene (PTEPM-b-PS) diblock copolymers can self-assemble and become cross-linked to form hollow spheres in situ with polystyrene on their inner surfaces. The addition of tetraethoxysilane (TEOS), which was hydrolyzed and condensed together with PTEPM block, can make those spheres as soft foldable capsules or hard hollow spheres depending on the amount of added TESO. Then postmodification, the surface-initiated Atom Transfer Radical Polymerization (ATRP) was applied to afford stimuli-responsive spheres, and the corresponding responsive Janus nanoplates (RJPs) were finally obtained by crushing those responsive hollow spheres (HSs) showing smart tunable emulsifiability and great potential in oily water purification. This facile method to fabricate HSs and RJPs could be used for preparing different Janus polymer-inorganic capsules and nanoplates with varied functions by changing the chemical composition of copolymer surfactants as well as the postmodification process.

Biomedically Relevant Self-Assembled Metallacycles and Metallacages.

Diverse metal-organic complexes (MOCs), shaped as rectangles, triangles, hexagons, prisms, and cages, can be formed by coordination between metal ions (Pt, Pd, Ru, Rh, Ir, Zn, Co, and Cd) and organic ligands, with potential applications as alternatives to conventional biomedical materials for therapeutic, sensing, and imaging purposes. MOCs have been investigated as anticancer drugs in the treatment of malignant tumors in lung, cervical, breast, colon, liver, prostate, ovarian, brain, stomach, bone, skin, mouth, thyroid, and other cancers. MOCs with one, two, and three cavities have also been investigated as drug carriers and prepared for the loading and release of different drugs. In addition, MOCs can target proteins by the shape effect and recognize sugars and DNA by electrostatic interactions, as well as estradiol by host-guest interactions, etc. This Perspective mainly covers achievements in the biomedical application of MOCs. We aim to identify some key trends in the reported MOC structures in relation to their biomedical activity and potential applications.

Self-Assembly of Metallacages into Multidimensional Suprastructures with Tunable Emissions.

Cubic metallacages were arranged into multidimensional (one-, two-, and three-dimensional) suprastructures via multistep assembly. Four new shape-controllable, hybrid metallacages with modified substituents and tunable electronic properties were prepared using dicarboxylate ligands with various substituents (sodium sulfonate, nitro, methoxyl, and amine), tetra-(4-pyridylphenyl) ethylene, and cis-(PEt3)2Pt(OTf)2. The as-prepared metallacages were used as building blocks for further assembly. Diverse suprastructures with tunable emissions (λmax from 451 to 519 nm) and various substituents (-SO3Na, -NO2, -OCH3, and -NH2) were prepared depending on the substituents and solvents used.

Biodegradable stimuli-responsive polypeptide materials prepared by ring opening polymerization.

The stimuli-responsive polypeptides have drawn extensive attention because of their promising applications in biotechnology considering their biocompatibility, biodegradability, and bioactivity. In this tutorial review, we summarize the most recent progress in this area, including thermo-, redox-, photo-, and biomolecule responsive polypeptides over the past decade. The design and synthesis of stimuli-responsive polypeptides will be briefly introduced. The correlation between the structure and properties, particularly the effects of polypeptide conformation, will be emphasized here. In addition, the applications of stimuli-responsive polypeptides in controlled drug release and tissue engineering are briefly discussed.

Janus Silica Hollow Spheres Prepared via Interfacial Biosilicification.

A poly(ethylene glycol)-b-poly(L-lysine)-b-poly(styrene) (PEG-PLL-PS) triblock copolymer, which contains a cationic PLL block as the middle block, is synthesized via a combination of ring-opening polymerization (ROP) and atom-transfer radical polymerization (ATRP). The PEG-PLL-PS (ELS) triblock is employed as a macromolecular surfactant to form a stable oil-in-water (O/W) emulsion, which is subsequently used as the template to prepare Janus silica hollow spheres (JHS) via a one-pot biosilicification reaction. For the emulsion template, the middle PLL block assembles at the O/W interface and directs the biomimetic silica synthesis in the presence of phosphate buffer and silicic acid precursors. This biosilicification process takes place only in the intermediate layer between water and the organic interior phase, leading to the formation of silica JHSs with hydrophobic PS chains tethered to the inner surface and PEG attached to the outer surface. The three-layer JHSs, namely, PEG/silica-polylysine/PS composites, were verified by electron microscopy. Upon further breaking these JHSs into species, polymer-grafted Janus silica nanoplates (JPLs) can be obtained. Our studies provide an efficient one-step method for preparing hybrid silica Janus structures within minutes.

Tuning the phase transition temperature of thermal-responsive OEGylated poly-L-glutamate via random copolymerization with L-alanine.

Two series of copolymers were prepared by ring-opening polymerization (ROP) of γ-(2-methoxyethoxy)esteryl-L-glutamate (L-EG2Glu) N-carboxyanhydride (NCA) and L-alanine (L-Ala) using HMDS and PEG-NH2 as initiator, respectively. Poly-(L-EG2Glu-co-L-Ala) displayed lower critical solution temperature (LCST) behavior but had a lower phase transition temperature than poly-L-EG2Glu at similar molecular weight (MW). The clouding point (CP) of random copolypeptides can be tuned by altering the alanine content and overall MW. Circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) indicated that the thermal-responsive properties depended on the content of ordered conformations. PEG-b-poly-(L-EG2Glu-co-L-Ala) can spontaneously form hydrogels in water at room temperature. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that these hydrogels were formed by nanoribbons. The intermolecular hydrogen bonding among copolypeptide blocks accounted for the nanoribbon assemblies and hydrogel network formation.

Hydrogels assembled from star-shaped polypeptides with a dendrimer as the core.

A second or fourth generation dendrimer with primary amine as the peripheral terminal group was first synthesized via Michael addition and thiol-yne addition. A series of star-shaped polypeptides was synthesized by ring opening polymerization (ROP) of γ-(2-(2-methoxyethoxy)ethyl) l-glutamate (l-EG2Glu) N-carboxyanhydride (NCA) using the amine group terminated dendrimer as the initiator. Taking advantage of the well-defined dendrimer and ROP, the arm number and arm length can be easily controlled. These star-shaped poly(l-EG2Glu) can spontaneously form hydrogels instead of micelles in water at low concentration. The critical gelation concentration (CGC) and hydrogel strength displayed a stronger dependence on arm numbers than the arm length under similar conditions. These properties can be easily modulated by varying the poly(l-EG2Glu) arm length and arm number. The hydrogels showed shear thinning and rapid recovery properties. TEM and AFM characterization revealed that the hydrogel networks were constituted by entangled and branched fibrils.

Tailorable aqueous dispersion of single-walled carbon nanotubes using tetrachloroperylene-based bolaamphiphiles via noncovalent modification.

The enhanced dispersing capability of these bolaamphiphiles can be attributed to the large aromatic perylene core. The aqueous dispersion efficiency of single-walled carbon nanotubes (SWCNTs) is investigated by UV-vis absorption, fluorescence emission and Raman spectra, scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. It is found that the tetrachloroperylene backbone moieties could interact with SWCNT via synergistic π-π and hydrophobic interactions, and the dispersing properties are closely related to the hydrophilic part of bolaamphiles. This study not only demonstrates tetrachloroperylene derivatives are able to stabilize SWCNTs, but also provides the possibility to understand the structure-property relationship between SWCNTs and tetrachloroperylene-based surfactants.

Thermally sensitive self-assembly of glucose-functionalized tetrachloro-perylene bisimides: from twisted ribbons to microplates.

Chiral supramolecular structures are becoming increasingly attractive for their specific molecular arrangements, exceptional properties, and promising applications in chiral sensing and separation. However, constructing responsive chiral supramolecular structures remains a great challenge. Here, glucose-functionalized tetrachloro-perylene bisimides (GTPBIs) with thermally sensitive self-assembly behaviors are designed and synthesized. In a methanol/water mixture, GTPBIs self-assembled into twisted ribbons and microplates at 4 and 25 °C, respectively. Furthermore, the ribbon structure was metastable and could transform into microplates when the temperature was increased from 4 to 25 °C. Transmission electron microscopy (TEM) was used to track the evolution of morphology and study the assembly mechanisms of correponding nanostructures at different time intervals. The supramolecular structures were characterized with various techniques, including circular dichroism, TEM, scanning electron microscopy, atomic force microscopy, ultraviolet-visible absorption, and fluorescence spectra. This study provides insight into controlling molecular parameters and assembly conditions to construct chiral supramolecular structures.

Fibril aggregates formed by a glatiramer-mimicking random copolymer of amino acids.

Amyloid formation is now considered a universal and intrinsic property of all proteins, irrespective of their sequences. Therefore, it is interesting to see whether random copolymers of amino acids can also form amyloid aggregates. Here we use a copolymer of 4 amino acids, mimicking the clinically used drug Glatiramer, and demonstrate that it does form amyloid-like fibrils in the aqueous solution despite its random sequence structure. The fibrillar aggregates show an alanine-rich ß-sheet secondary structure, proving the high tolerance of amyloid aggregates to the sequence irregularity in poly(amino acid)s, and suggesting the potential application of random copolymers as amyloid materials.

Oxidation-responsive OEGylated poly-L-cysteine and solution properties studies.

The oxidation-responsive behaviors of OEGylated poly-L-cysteine homopolypeptides, that is, poly(L-EG(x)MA-C)n, were investigated. These poly-L-cysteine derivatives adopted mixed conformation in water, in which the ß-sheet accounted for a significant proportion. Upon oxidation, the thioethers in polypeptide side chains were converted to polar sulfone groups, which triggered the secondary structure transition from ß-sheet preferred conformation to random coil. Accordingly, the increase of side-chain polarity together with conformation changes increased samples' water solubility and cloud point temperature. Using mPEG45-NH2 as macroinitiator, we synthesized PEG45-b-poly(L-EG2MA-C)22 diblock copolymer via ring-opening polymerization (ROP) of L-EG2MA-C N-carboxyanhydride (NCA). The PEG45-b-poly(L-EG2MA-C)22 was able to self-assemble into spherical micelles in aqueous solution, and the micelles could undergo an oxidation-triggered disassembly due to the oxidation-responsive thioethers. Such a new class of oxidation-responsive polypeptides might provide a promising platform to construct inflammation targeting drug delivery systems.

Tracking the effects of PLGA-based nanoparticles on protein expression in living cells through quantitative proteomics.

Mass spectrometry (MS)-based proteomics can identify and quantify the differential abundance of expressed proteins in parallel, and bottom-up proteomic approaches are even approaching comprehensive coverage of the complex eukaryotic proteome. Protein-nanoparticle (NP) interactions have been extensively studied owing to their importance in biological applications and nanotoxicology. However, the proteome-level effects of NPs on cells have received little attention, although changes in protein abundance can reflect the direct effects of nanocarriers on protein expression. Herein, we investigated the effect of PLGA-based NPs on protein expression in HepG2 cells using a label-free quantitative proteomics approach with data independent acquisition (DIA). The percentage of two-fold change in the protein expression of cells treated with PLGA-based NPs was less than 10.15% during a 6 hour observation period. Among the changed proteins, we found that dynamic proteins involved in cell division, localization, and transport are more likely to be more susceptible to PLGA-based NPs.

Risk stratification of papillary thyroid cancers using multidimensional machine learning.

BACKGROUND: Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics. MATERIALS AND METHODS: The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system. RESULTS: The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively. CONCLUSION: This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.

Conformation-specific self-assembly of thermo-responsive poly(ethylene glycol)-b-polypeptide diblock copolymer.

Poly(ethylene glycol)-block-poly(γ-(2-methoxyethoxy)esteryl-L-glutamate) (PEG-b-poly-L-EG2Glu) was synthesized via ring-opening polymerization (ROP) of L-EG2Glu N-carboxyanhydride (NCA) using PEG-NH2 as macroinitiator. This diblock contained a thermo-responsive poly-L-EG2Glu block, which adopted primarily helical conformation in pristine aqueous solution. We found that PEG-b-poly-L-EG2Glu diblock can display two levels of self-assembly behaviors associated with hydrophobic interactions and conformation-specific reassembly, respectively. Upon temperature increase, the PEG-b-poly-L-EG2Glu diblock formed wormlike micelles, in which the poly-L-EG2Glu formed the micelle core and maintained helical conformation. However, extension of thermal annealing time drove the secondary structure transformation of the poly-L-EG2Glu block from helical conformation to ß-sheet, which accounted for an assembly structure transition from wormlike micelles to nanoribbons. The critical factor was that poly-L-EG2Glu block can undergo thermo-induced hydrophobicity and conformation transformation, which offered an additional parameter to tune the nature of molecular interactions, i.e., intermolecular versus intramolecular hydrogen bonding interactions. The corresponding conformation and assembly structure changes were characterized using FTIR and electron microscopy, respectively.

Peptide hydrogels assembled from nonionic alkyl-polypeptide amphiphiles prepared by ring-opening polymerization.

Three alkyl-polypeptide (AP) amphiphiles were prepared using ring-opening polymerization of α-amino acid N-carboxyanhydride. The polypeptide segment was composed of diethylene-glycol-monomethyl-ether-functionalized poly-L-glutamate (poly-L-EG(2)Glu). These AP amphiphiles can spontaneously self-assemble into transparent hydrogels in water. These hydrogels showed shear thinning properties, and their strength can be modulated by hydrophobic alkyl tails. CryoTEM and AFM characterizations suggested that these hydrogels were formed by nanoribbons arising from intermolecular interactions between nonionic poly-L-EG(2)Glu segments.

A humidity-resistant bio-inspired microfibrillar adhesive fabricated using a phenyl-rich polysiloxane elastomer for reliable skin patches.

Steady adhesion under varying humidity conditions is fundamentally challenging due to the barrier of interfacial water molecules. Here, we demonstrate a humidity-resistant gecko-inspired microfibrillar adhesive fabricated by using a specific phenyl-rich polysiloxane. In contrast with the great decline of macroadhesion with increasing humidity for the typical polydimethylsiloxane (PDMS) microfibrillar adhesives, strong macroadhesion of a microfibrillar adhesive fabricated using synthetic phenyl-rich polysiloxane maintains adhesion well across a wide relative humidity range (1% to 95%). Moreover, the pull-off strength is increased by 500% compared to that of phenyl-absent PDMS microfibrillar adhesives at extremely high humidity. Mechanism analysis demonstrates that the synergistic interplay of strong interfacial hydrophobicity leading to dry contact and bulk energy dissipation through massive aromatic π-π interactions contributes greatly to the reliable and strong humidity macroadhesion. The present results provide a better understanding of humidity macroadhesion as well as application potential for microfibrillar adhesives, which are proven to be reliable skin adhesive patches for long-term health-care that have to be exposed to varying humidity conditions of the skin surface.

Proteotypic Differences of Follicular-Patterned Thyroid Neoplasms.

The diagnosis of follicular-patterned thyroid tumors such as follicular thyroid adenoma (FA), follicular thyroid carcinoma (FTC), and follicular variant of papillary thyroid carcinoma (FvPTC) remains challenging. This study aimed to explore the molecular differences among these three thyroid tumors by proteomic analysis. A pressure cycling technology (PCT)-data-independent acquisition (DIA) mass spectrometry workflow was employed to investigate protein alterations in 52 formalin-fixed paraffin-embedded (FFPE) specimens: 18 FA, 15 FTC, and 19 FvPTC specimens. Immunohistochemical (IHC) analysis of 101 FA, 67 FTC, and 65 FvPTC specimens and parallel reaction monitoring (PRM) analysis of 20 FA, 20 FTC, and 20 FvPTC specimens were performed to validate protein biomarkers. A total of 4107 proteins were quantified from 52 specimens. Pairwise comparisons identified 287 differentially regulated proteins between FTC and FA, and 303 between FvPTC and FA and 88 proteins were co-dysregulated in the two comparisons. However, only 23 discriminatory proteins between FTC and FvPTC were detected. Additionally, the quantitative results for ANXA1 expression based on IHC staining and PRM-MS quantification were consistent with the proteomic results, showing that ANXA1 can be used to distinguish FvPTC from FA and FTC. The differentially regulated proteins found in this study can differentiate FA from FvPTC. In addition, ANXA1 is a promising biomarker for differentiating FvPTC from the other thyroid tumors.