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Because of the steady increase in multi-drug-resistant bacterial infections, we developed a viable treatment strategy using new antibacterial nanomaterials with photosensitizing effects. In this work, three triphenylamine derivates (TPA-2PE, TPA-PCN, and TPA-2PCN) and amphiphilic polystyrene maleic anhydride (PSMA) were used to successfully prepare three corresponding nanoparticles. Compared to TPA-2PE, the introduced cyano unit resulted in a redshift for TPA-PCN and TPA-2PCN with near-infrared (NIR) emission. The specific aggregation-induced emission (AIE) characteristic contributed to the retentive photophysical property and the increased fluorescence quantum yield (QY) of these luminous molecules in nanoparticles. Our in vitro study indicated that the nanoparticles were able to tightly bind to the surface of bacteria by hydrogen bond interaction, and their bacterial toxicity was successfully directed against antibiotic-resistant Escherichia coli. The bactericidal performance was further amplified under white light irradiation by the supplied photosensitizing effect. Additionally, the killed bacteria were stained with the nanoparticles and subsequently emitted NIR emission, regardless of the interference of bacterial autofluorescence. The sterilization effects of the nanoparticles were tracked in situ and qualitatively characterized by the NIR self-reporting function. In the protocol reported herein, we describe all the essential factors for addressing antibiotic resistance, and therefore, this work includes all the necessary criteria for designing additional antibacterial nanomaterials in the future.

Solar-to-chemical energy conversion by photocatalytic hydrogen evolution (PHE) is critical for reduction of the pollution and storage of clean energy. To improve the solar conversion efficiency, it is highly imperative to accelerate the photocarrier separation and transportation through materials design. Herein, we describe a highly effective PHE catalyst based on in-plane benzene-ring doped g-C3N4 nanosheets heterostructure through the thermal co-polymerization of urea and 4, 4'-sulfonyldiphenol (BPS) followed by a controlled heat-etching step. The solid-state 13C NMR confirms the existence of benzene-ring structure in g-C3N4 nanosheets. Experimental results and theoretical calculations show that the energy and electronic structure of the catalyst are optimally regulated, inducing increased light absorption and effectively accelerated separation of the photo-driven charge carriers. It exhibits enhanced photocatalytic hydrogen evolution efficiency with a PHE rate of 12.3 mmol h−1 g−1 (almost 12 times higher than that of pure g-C3N4 nanosheets) and the quantum efficiency of 17.7% at 420 nm.

3D printing of stem cells provides a tremendous opportunity to tissue engineering in regenerative medicine. However, developing new bioactive materials to rationally augment stem cell viability is still an enormous challenge owing to the nutritionally deficient environment caused by the limited-penetration distance of nutrition when cells are encapsulated within biomaterials. In this work, a cationic conjugated polythiophene derivative, poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride] (PMNT), is designed and integrated into an anionic gelatin/alginate matrix to develop a new 3D bioprintable conjugated polymer ink Gel/Alg/PMNT, while the electrostatic interaction can assist PMNT to anchor inside ink without severe diffusional loss. In principle, PMNT is confirmed to promote human umbilical cord-derived mesenchymal stem cell (hMSC) proliferation in a serum-free medium by driving cell cycles and up-regulating gene expression in the pathways of biosynthesis and the metabolism. By employing the 3D bioprinting strategy together with hMSCs, the accelerated healing of full-thickness excisional wounds is further realized through the augmented-stem cell therapeutics utilizing Gel/Alg/PMNT ink, in which hMSC proliferation can be effectively promoted upon inductive stimulation of PMNT. The inherent highly bioactive and robust proliferation-promoted nature of the developed conjugated polymer ink Gel/Alg/PMNT significantly overcomes the nutritionally deficient environment, especially in 3D-printed large-scale architectures. The bioactive polythiophene material exhibits a unique capacity to promote stem cell proliferation without the need of serum, providing a new bioink for 3D bioprinting in tissue reconstructions.

Peptide surfactants have shown many potential applications in biology and medicine; however, the mechanism of their interactions with biomembranes is still unclear. This work has studied the interactions of cationic peptide gemini surfactants based on lysine spacers (12-(Lys)n-12, n = 2, 4, and 6) with model biological membranes, which are represented by the vesicles separately formed by zwitterionic unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic unsaturated phospholipid 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG, sodium salt) and the DOPC/DOPG (1 : 1) mixture. The experiment results show that the presence of negatively charged DOPG slightly affects the interaction manners of 12-(Lys)n-12 with the vesicles, while the interaction of 12-(Lys)2-12 with the phospholipid vesicles is significantly different from that of 12-(Lys)4-12 and 12-(Lys)6-12 with the vesicles. The binding strength decreases in the order of 12-(Lys)4-12 > 12-(Lys)6-12 > 12-(Lys)2-12. The 12-(Lys)4-12 surfactant solubilizes the DOPC vesicles, and makes the DOPC molecules join the surfactant stiff fibers and changes them into long and flexible wormlike micelles, while the 12-(Lys)6-12 and 12-(Lys)2-12 aggregates are disassembled by the DOPC vesicles, and the surfactant molecules join the DOPC vesicles and convert the unilamellar vesicles into multilamellar vesicles. This work should be helpful in understanding the interaction of peptide surfactants with phospholipid membranes.

To address the challenge from microbial resistance and biofilm, this work develops three gemini peptide amphiphiles with basic tetrapeptide spacers 12-(Arg)4-12, 12-(Lys)4-12, and 12-(His)4-12 and finds that they exhibit varied antimicrobial/antibiofilm activities. 12-(Arg)4-12 shows the best performance, possessing the broad-spectrum antimicrobial activity and excellent antibiofilm capacity. The antimicrobial and antibiofilm activities strongly depend on the membrane permeation and self-assembling structure of these peptide amphiphiles. Gemini peptide amphiphile with highly polar arginine as the spacer, 12-(Arg)4-12, self-assembles into short rods that are prone to dissociate into monomers for permeating and lysing membrane , leading to its broad-spectrum antimicrobial activity and high efficiency in eradicating biofilm. Long rods formed by relatively weaker polar 12-(Lys)4-12 are less prone to disassemble into monomers for further membrane permeation, which makes it selectively kill more negatively charged bacteria and endow it medium antibiofilm activity. Low polar 12-(His)4-12 aggregates into long fibers, which are very difficult to dissociate and they mainly electrostatically bind on the negative microbial surface, resulting in its weakest antimicrobial and antibiofilm activity. This study reveals the effect of the antimicrobial peptide structure and aggregation on the antimicrobial activities and would be helpful for developing high-efficient antimicrobial peptides with antibiofilm activity.

Gemini-type peptide amphiphiles 12-(Lys)n-12 (n = 2, 4, 6) with different lysine spacer lengths have been established and exhibit excellent antibacterial activities. By varying the lysine number in the spacer, the distinct aggregates with zero- to three-dimensional structures (fibers, short rods, and spherical aggregates) are formed. These different length/diameter ratios of aggregates have great effects on the antibacterial activities and cytotoxicity. 12-(Lys)2-12 has a relatively higher minimal inhibitory concentration (MIC) value and shows toxicity toward mammalian cells just above its MIC value, while 12-(Lys)4-12 and 12-(Lys)6-12 have lower MIC values and no cytotoxicity even at 5 times the MIC values.

Peptide amphiphiles (PAs) can self-assemble into a variety of supramolecular structures with excellent biofunctions. However, their assembly with time has rarely been observed and reported. Here, we find that a novel gemini-type PA [12-(Lys)2-12], taking two lysine (Lys) groups as the spacer, shows an obvious assembly and evolution process with time. Driven by the strong hydrophobic interaction between the alkyl chains as well as the electrostatic force and hydrogen bonding among the peptide spacers, the 12-(Lys)2-12 molecules first self-assemble into vesicles and then transform into fibrils, ribbons, and belts with time. If replacing the -(Lys)2- spacer with four lysine groups [-(Lys)4-] or two glutamic acid groups [-(Glu)2-], the PA molecules do not show the aggregate growth with time. This indicates that the lysine structure and its length are important structural factors contributing to the dynamic aggregate evolution behavior. More interestingly, this assembly and evolution behavior is highly dependent on 12-(Lys)2-12 concentration. Only in the proper concentration region (0.5-0.7 mM), the self-assembly displays the aggregate growth with time. At lower or higher concentrations, the aggregate growth is largely delayed or inhibited. Moreover, we also find that the aggregate growth of 12-(Lys)2-12 is related to the fibril solubilization temperature ( Tf→s). The faster aggregate growth occurs when the temperature is much lower than Tf→s. This work gains new insights into the evolution of the self-assembling structures of peptide amphiphiles.

It is important to develop efficient therapeutic methods to maintain a healthy balance among gut microbiota by increasing the beneficial bacteria and decreasing the harmful bacteria. In this work, a cationic polythiophene derivative poly(3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride) (PMNT) with quaternary ammonium groups as side chains has been used for efficiently promoting the initial adhesion and biofilm formation of beneficial bacteria in gut microbiota. Upon addition of PMNT, three species of gut microbiota have an increased biofilm formation ability (216.5 % for Escherichia coli (E. coli), 130.7 % for Bifidobacterium infantis (B. infants) and 47.6 % for Enterococcus faecalis (E. faecalis)). As the initial adhesion of bacteria to a surface is an essential step during biofilm formation, PMNT can promote the attachment of bacteria by forming bacteria /PMNT aggregates which possess more cell-to-cell interactions. RNA sequencing results of bacteria within biofilm indicate that the utilization of carbohydrate and glycan is accelerated in the presence of PMNT, leading to enhanced quorum sensing and biofilm formation of E. coli. After forming biofilm, beneficial bacteria have an enhanced resistance to adverse environmental conditions which is significant for maintaining the balance of gut microbiota. Conjugated polymers exhibit a good potential application in modulating the balance of gut microbiota and development of new probiotics drugs.

A series of surfactant-like peptides have been designed for inducing DNA condensation, which are all comprised of the same set of amino acids in different sequences. Results from experiments and molecular dynamics simulations show that the peptide’s self-assembly and DNA-interaction behaviors can be well manipulated through sequence variation. With optimized pairing modes between the β-sheets, the peptide of I3V3A3G3K3 can induce efficient DNA condensation into virus-mimicking structures. The condensation involves two steps; the peptide molecules first bind onto the DNA chain through electrostatic interactions and then self-associate into β-sheets under hydrophobic interactions and hydrogen bonding. In such condensates, the peptide β-sheets act as scaffolds to assist the ordered arrangement of DNA, mimicking the very nature of the virus capsid in helping DNA packaging. Such a hierarchy affords an extremely stable structure to attain the highly condensed state and protect DNA against enzymatic degradation....

This work involved the construction of pH-responsive self-assembly systems from a pH-sensitive four-arm carboxylate acid (4EOCOOH) and either the cationic single chain surfactant dodecyl trimethyl ammonium bromide (DTAB) or the cationic gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12). It was found that the constructed oligomeric-like structures from the mixtures of 4EOCOOH with DTAB or 12-6-12 greatly enhance the aggregation ability of the mixtures, thus improving the pH-responsivity. In particular, surfactant concentrations significantly affect the pH-responsivity at a fixed 4EOCOOH concentration. At higher surfactant concentrations, the pH-responsivity is suppressed, while at lower surfactant concentrations, the mixed aggregates gradually change from micelles to unstable large spherical aggregates or vesicles, and then to stable spherical aggregates, with decreasing pH. Moreover, the surfactant/4EOCOOH systems have different solubilization abilities for three hydrophobic drugs. For quercetin and baicalein, the systems support much better solubilization at lower pH values, while for indomethacin, the systems show better solubilization at higher pH values. In particular, compared with DTAB, 12-6-12 is more efficient in constructing pH-responsive systems, and the 12-6-12/4EOCOOH mixture shows better ability for solubilizing hydrophobic drugs. This work will be helpful in the design of high-efficiency, pH-responsive surfactant systems for solubilizing hydrophobic drugs by simply mixing pH-sensitive molecules with surfactants.

A star-shaped oligomeric-like surfactant with variable oligomeric degrees has been formed with a four-arm carboxylate salt (4EOCOONa) and cationic single chain surfactant dodecyl trimethylammonium bromide (DTAB). The aggregation of the 4EOCOONa/(DTAB)n complexes has been investigated by surface tension, electrical conductivity, isothermal titration microcalorimetry, ζ potential, dynamic light scattering, 1H NMR spectroscopy, and steady-state fluorescence measurements. The calorimetric result shows that 4EOCOONa interacts strongly with DTAB and each 4EOCOONa molecule binds with six DTAB molecules, wherein four DTAB molecules electrostatically bind to one 4EOCOONa molecule and additional two DTAB molecules further bind to the 4EOCOONa/(DTAB)n complex by hydrophobic interaction. The critical micelle concentration (CMC) of the 4EOCOONa/(DTAB)n complexes is remarkably lower than the CMC of DTAB, similar to synthesized star-shaped oligomeric surfactants. The micelle properties of the DTAB/4EOCOONa mixtures depe...