Self-assembly In Water Research Articles

Amphiphilic Single-Chain Polymer Nanoparticles as Imaging and Far-Red Photokilling Agents for Photodynamic Therapy in Zebrafish Embryo Xenografts.

This work introduces rationally designed, improved amphiphilic single-chain polymer nanoparticles (SCNPs) for imaging and photodynamic therapy (PDT) in zebrafish embryo xenografts. SCNPs are ultrasmall polymeric nanoparticles with sizes similar to proteins, making them ideal for biomedical applications. Amphiphilic SCNPs result from the self-assembly in water of isolated synthetic polymeric chains through intrachain hydrophobic interactions, mimicking natural biomacromolecules and, specially, proteins (in size and when loaded with drugs, metal ions or fluorophores also in function). These ultrasmall, soft nanoparticles have various applications, including catalysis, sensing, and nanomedicine. Initial in vitro experiments with nonfunctionalized, amphiphilic SCNPs loaded with a photosensitizing Zn phthalocyanine with four nonperipheral isobutylthio substituents, ZnPc, showed promise for PDT. Herein, the preparation of improved, amphiphilic SCNPs containing ZnPc as highly efficient photosensitizer encapsulated within the nanoparticle and surrounded by anthracene units is disclosed. The amount of anthracene groups and ZnPc molecules within each single-chain nanoparticle controls the imaging and PDT properties of these nanocarriers. Critically, this work opens the way to improved PDT applications based on amphiphilic SCNPs as a first step toward ideal, long-term artificial photo-oxidases (APO).

Intrinsically reactive hyperbranched interface governs graphene oxide dispersion and crosslinking in epoxy for enhanced flame retardancy

Enhancing the flame retardancy of epoxy (EP) resins typically entailed a trade-off with other physical properties. Herein, hyperbranched poly(amidoamine) (HPAA) and phytic acid (PA) were used to functionalize graphene oxide (GO) via electrostatic self-assembly in water to prepare a phosphorus-nitrogen functionalized graphene oxide nanosheet (PN-GOs), which could be utilized as high efficient flame-retardant additive of epoxy resin without sacrificing other properties. The PN-GOs demonstrated improved dispersion and compatibility within the EP matrix, which resulted in significant concurrent enhancements in both the mechanical performance and flame-retardant properties of the PN-GOs/EP nanocomposites over virgin EP. Notably, the incorporation of just 1.0 wt% PN-GOs yielded a 20.4, 6.4 and 42.7 % increases in flexural strength, flexural modulus and impact strength for the PN-GOs/EP nanocomposites, respectively. Furthermore, simultaneous reductions were achieved in the peak heat release rate (pHRR) by 60.0 %, total smoke production (TSP) by 43.0 %, peak CO production rate (pCOP) by 57.9 %, and peak CO2 production rate (pCO2P) by 63.9 %. This study presented a facile method for the design of GO-based nano flame retardants, expanding their application potential in polymer-matrix composites.

Photo-Induced Disproportionation-Mediated Photodynamic Therapy: Simultaneous Oxidation of Tetrahydrobiopterin and Generation of Superoxide Radicals.

We herein present an approach of photo-induced disproportionation for preparation of Type-I photodynamic agents. As a proof of concept, BODIPY-based photosensitizers were rationally designed and prepared. The photo-induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4 ), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2 - ⋅). One of our Type-I photodynamic agents not only self-assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2 ), with a half-maximal inhibitory concentration (IC50 ) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors.

Self-assembled Janus base nanotubes: chemistry and applications.

Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and π-π stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while π-π interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water.

Glycyrrhizic acid aggregates seen from a synthetic surfactant perspective.

Bio- or plant-based surfactants are a sustainable and renewable alternative to replace synthetic chemicals for environmental, drugs and food applications. However, these "green" surfactants have unique molecular structures, and their self-assembly in water might lead to complex morphologies and unexpected properties. The micellization of saponin molecules, such as glycyrrhizic acid (GA), differs significantly from those of conventional synthetic surfactants, yet these differences are often overlooked. Saponins self-assemble in complex hierarchical helical morphologies similar to bile salts, rather than the expected globular, ellipsoidal and wormlike micelles. Here, we review two potential routes for molecular self-assembly of GA, namely kinetics of crystallization and thermodynamic equilibrium, focusing on their structure as a function of concentration. Some uncertainty remains to define which route is followed by GA self-assembly, as well as the first type of aggregate formed at low concentrations, thus we review the state-of-the-art information about GA assembly. We compare the self-assembly of GA with conventional linear surfactants, and identify their key similarities and differences, from molecular and chemical perspectives, based on the critical packing parameter (CPP) theory. We expect that this work will provide perspectives for the unclear process of GA assembly, and highlight its differences from conventional micellization.

J-Aggregate-Triggering BODIPYs: an Ultrasensitive Chromogenic and Fluorogenic Sensing Platform for Perfluorooctanesulfonate.

Contamination of water supplies by polyfluoroalkyl substances, notably perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), has serious health and environmental consequences. Therefore, the development of straightforward and effective means of monitoring and removing PFASs is urgently required. In this study, we report a rapid and sensitive method for the detection of PFOS and PFOA in water that rely on the J-aggregate formation of meso-ester-BODIPY dyes. The dye C10-mim, which contains a hydrophilic methylimidazolium group and a hydrophobic alkylated BODIPY, self-assembles in water into weakly green-emissive micellar assemblies. Upon binding to PFOS or PFOA, a spontaneous disassembly and reorganization forms orange-emissive J-aggregates. The rapid formation (≤5 s) of J-aggregates and the accompanying spectral shifts provide a superior sensing performance, with excellent sensitivity (limit of detection=0.18 ppb for PFOS) and distinct chromogenic and fluorogenic "turn-on" responses.

Geometric Transformations Afforded by Rotational Freedom in Aramid Amphiphile Nanostructures.

Molecular self-assembly in water leads to nanostructure geometries that can be tuned owing to the highly dynamic nature of amphiphiles. There is growing interest in strongly interacting amphiphiles with suppressed dynamics, as they exhibit ultrastability in extreme environments. However, such amphiphiles tend to assume a limited range of geometries upon self-assembly due to the specific spatial packing induced by their strong intermolecular interactions. To overcome this limitation while maintaining structural robustness, we incorporate rotational freedom into the aramid amphiphile molecular design by introducing a diacetylene moiety between two aramid units, resulting in diacetylene aramid amphiphiles (D-AAs). This design strategy enables rotations along the carbon-carbon sp hybridized bonds of an otherwise fixed aramid domain. We show that varying concentrations and equilibration temperatures of D-AA in water lead to self-assembly into four different nanoribbon geometries: short, extended, helical, and twisted nanoribbons, all while maintaining robust structure with thermodynamic stability. We use advanced microscopy, X-ray scattering, spectroscopic techniques, and two-dimensional (2D) NMR to understand the relationship between conformational freedom within strongly interacting amphiphiles and their self-assembly pathways.

Synthesis of Oxazoline/Methacrylate-Based Graft-Copolymers via Grafting-Through Method and Evaluation of Their Self-Assembly in Water and Dodecane

Synthesis of Oxazoline/Methacrylate-Based Graft-Copolymers <i>via</i> Grafting-Through Method and Evaluation of Their Self-Assembly in Water and Dodecane

Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot.

Nonionic hydrogels are of particular interest for long-term therapeutic implantation due to their minimal immunogenicity relative to their charged counterparts. However, in situ formation of nonionic supramolecular hydrogels under physiological conditions has been a challenging task. In this context, we report on our discovery of salt-triggered hydrogelation of nonionic supramolecular polymers (SPs) formed by self-assembling prodrug hydrogelators (SAPHs) through the Hofmeister effect. The designed SAPHs consist of two SN-38 units, which is an active metabolite of the anticancer drug irinotecan, and a short peptide grafted with two or four oligoethylene glycol (OEG) segments. Upon self-assembly in water, the resultant nonionic SPs can be triggered to gel upon addition of phosphate salts. Our 1 H NMR studies revealed that the added phosphates led to a change in the chemical shift of the methylene protons, suggestive of a disruption of the water-ether hydrogen bonds and consequent reorganization of the hydration shell surrounding the SPs. This deshielding effect, commensurate with the amount of salt added, likely promoted associative interactions among the SAPH filaments to percolate into a 3D network. The formed hydrogels exhibited a sustained release profile of SN-38 hydrogelator that acted potently against cancer cells.

An EGCG-mediated self-assembled micellar complex acts as a bioactive drug carrier.

Epigallocatechin gallate (EGCG) has attracted the increasing attention of many researchers, especially in the field of tumor therapy. However, EGCG has poor fat solubility, low stability, low bioavailability, and a high effective dose in vivo. Traditional drug delivery methods are difficult to deliver the water-soluble EGCG efficiently and in high doses to tumor sites. To address these issues, a new type of strategy has been tried in this study to transform EGCG from a "Bioactive natural ingredient" into a "Bioactive drug carrier". Briefly, the EGCG was modified with a fat-soluble 9-fluorene methoxy carbonyl (Fmoc) motif, and the obtained EGCG-Fmoc showed a considerable improvement in lipid solubility and stability. Interestingly, EGCG-Fmoc obtained the characteristic of self-assembly in water, making it easier to take up by tumor cells. Furthermore, the self-assembled nanocomplex exhibited paclitaxel encapsulation performance and could achieve the dual delivery of EGCG and paclitaxel.

Temperature-Responsive Lactic Acid-Based Nanoparticles by RAFT-Mediated Polymerization-Induced Self-Assembly in Water.

This work demonstrates for the first-time biobased, temperature-responsive diblock copolymer nanoparticles synthesized by reversible addition-fragmentation chain-transfer (RAFT) aqueous emulsion polymerization-induced self-assembly (PISA). Here, monomers derived from green solvents of the lactic acid portfolio, N,N-dimethyl lactamide acrylate (DMLA) and ethyl lactate acrylate (ELA), were used. First, DMLA was polymerized by RAFT aqueous solution polymerization to produce a hydrophilic PDMLA macromolecular chain transfer agent (macro-CTA), which was chain extended with ELA in water to form amphiphilic PDMLA-b-PELA diblock copolymer nanoparticles by RAFT aqueous emulsion polymerization. PDMLAx homopolymers were synthesized targeting degrees of polymerization, DPx from 25 to 400, with relatively narrow molecular weight dispersities (Đ < 1.30). The PDMLA64-b-PELAy diblock copolymers (DPy = 10-400) achieved dispersities, Đ, between 1.18 and 1.54 with two distinct glass transition temperatures (Tg) identified by differential scanning calorimetry (DSC). Tg(1) (7.4 to 15.7 °C) representative of PELA and Tg(2) (69.1 to 79.7 °C) of PDMLA. Dynamic light scattering (DLS) studies gave particle z-average diameters between 11 and 74 nm (PDI = 0.04 to 0.20). Atomic force microscopy (AFM) showed evidence of spherical particles when dispersions were dried at ∼5 °C and film formation when dried at room temperature. Many of these polymers exhibited a reversible lower critical solution temperature (LCST) in water with a concomitant increase in z-average diameter for the PDMLA-b-PELA diblock copolymer nanoparticles.

Effect of Glycosylation on Self-Assembly of Lipid A Lipopolysaccharides in Aqueous Solutions.

Lipopolysaccharides (LPSs) based on lipid A produced by bacteria are of interest due to their bioactivity in stimulating immune responses, as are simpler synthetic components or analogues. Here, the self-assembly in water of two monodisperse lipid A derivatives based on simplified bacterial LPS structures is examined and compared to that of a native Escherichia coli LPS using small-angle X-ray scattering and cryogenic transmission electron microscopy. The critical aggregation concentration is obtained from fluorescence probe experiments, and conformation is probed using circular dichroism spectroscopy. The E. coli LPS is found to form wormlike micelles, whereas the synthetic analogues bearing six lipid chains and with four or two saccharide head groups (Kdo2-lipid A and monophosphoryl lipid A) self-assemble into nanosheets or vesicles, respectively. These observations are rationalized by considering the surfactant packing parameter.

Self-assembling NBD-tripeptide as a dual-mode colorimetric platform for naked eye and smartphone joint detection of micro to nanomolar Copper(II) ions

Compared to conventionally synthesized organic compounds, peptides with amphiphiles have unique advantages, especially in self-assembly. Herein, we reported a peptide-based molecule rationally designed for the visual detection of copper ions (Cu2+) in multiple modes. The peptide exhibited excellent stability, high luminescence efficiency, and environmentally responsive molecular self-assembly in water. In the presence of Cu2+, the peptide undergoes an ionic coordination interaction and a coordination-driven self-assembly process that leads to the quenching of fluorescence and the formation of aggregates. Therefore, the concentration of Cu2+ can be determined by the residual fluorescence intensity and the color difference between peptide and competing chromogenic agents before and after Cu2+ incorporation. More importantly, this variation in fluorescence and color can be presented visually, thus allowing qualitative and quantitative analysis of Cu2+ based on the naked eye and smartphones. Overall, our study not only extends the application of self-assembling peptides but also provides a universal method for dual-mode visual detection of Cu2+, which would significantly promote point-of-care testing (POCT) of metal ions in pharmaceuticals, food, and drinking water.

Random ionic polymers: Salt-triggered reversible vesicular self-assembly in water

NaCl salt as an external stimulus triggers the self-assembly of ionic polymers and offers a convenient route to structuring vesicular reversible polymeric nanoparticles. In this contribution, amphiphilic random imidazolium ionic polymers are synthesized by roping the partial anion exchange and the choice of N-substituent. These polymers are evaluated for their self-assembly behavior in water, and it is strengthened by dye encapsulation application in water through self-assembly. The effects of salt and pH study demonstrated the reversibility of self-assembly. The self-assembled nano-aggregates are thermoresponsive at the upper critical solution temperature (UCST) (Cp 47 °C). The synergic balance between hydrogen bonding and ionic self-assembly is attributed to the constituents in the macromolecular structure, making these polyionic liquids (PILs) a “smart” responsive system in water upon the addition of external stimuli, such as NaCl and KPF6. This self-assembly is acquired with partial anion exchange and salt balance in the water. The unusual interfacial activity of polymer to form a regular shape eventually to surfaces organic dye molecule serving as a type of stabilizer or scavenger evidenced by nano-size and vesicular morphology analysis.

Supramolecular Linear-Dendritic Nanoreactors: Synthesis and Catalytic Activity in “Green” Suzuki-Miyaura Reactions

This study describes the synthesis of novel amphiphilic linear-dendritic block copolymers and their self-assembly in water to form supramolecular nanoreactors capable of catalyzing Suzuki-Miyaura coupling reactions under "green" conditions. The block copolymers were formed through copper(I)-catalyzed alkyne-azide cycloaddition between azide functionalized poly(benzyl ether) dendrons as the perfectly branched blocks, as well as bis-alkyne modified poly(ethylene glycol), PEG, as the linear block. A first-generation poly(benzyl ether) dendron (G1) was coupled to a bis-alkyne modified PEG with molecular mass of 5 kDa, forming an ABA copolymer (G1)2-PEG5k-(G1)2 (yield 62%), while a second-generation dendron (G2) was coupled to a 11 kDa bis-alkyne modified PEG to produce (G2)2-PEG11k-(G2)2 (yield 49%). The structural purity and low dispersity of the linear-dendritic copolymers were verified by size-exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Their self-assembly was studied by dynamic light scattering, showing that (G1)2-PEG5k-(G1)2 and (G2)2-PEG11k-(G2)2 formed single populations of micelles (17 nm and 37 nm in diameter, respectively). The triazole rings located at the boundaries between the core and the corona are efficient chelating groups for transition metals. The ability of the micelles to complex Pd was confirmed by 1H NMR, transmission electron microscopy, and inductively coupled plasma. The catalytic activity of the supramolecular linear-dendritic/Pd complexes was tested in water by model Suzuki-Miyaura reactions in which quantitative yields were achieved within 3 h at 40 °C, while, at 17 °C, a yield of more than 70% was attained after 17 h.

Fragmentation of DMPC Membranes by a Wedge-Shaped Amphiphilic Cyclodextrin into Bicellar-like Aggregates.

Small bilayer lipid aggregates such as bicelles provide useful isotropic or anisotropic membrane mimetics for structural studies of biological membranes. We have shown previously by deuterium NMR that a wedge-shaped amphiphilic derivative of trimethyl βcyclodextrin anchored in deuterated DMPC-d27 bilayers through a lauryl acyl chain (TrimβMLC) is able to induce magnetic orientation and fragmentation of the multilamellar membranes. The fragmentation process fully detailed in the present paper is observed with 20% cyclodextrin derivative below 37 °C, where pure TrimβMLC self-assembles in water into large giant micellar structures. After deconvolution of a broad composite 2H NMR isotropic component, we propose a model where the DMPC membranes are progressively disrupted by TrimβMLC into small and large micellar aggregates depending whether they are extracted from the outer or inner layers of the liposomes. Below the fluid-to-gel transition of pure DMPC-d27 membranes (Tc = 21.5 °C), the micellar aggregates vanish progressively until complete extinction at 13 °C, with a probable release of pure TrimβMLC micelles leaving lipid bilayers in the gel phase doped with only a small amount of the cyclodextrin derivative. Bilayer fragmentation between Tc and 13 °C was also observed with 10% and 5% of TrimβMLC, with NMR spectra suggesting possible interactions of micellar aggregates with fluid-like lipids of the Pβ' ripple phase. No membrane orientation and fragmentation was detected with unsaturated POPC membranes, which are able to accommodate the insertion of TrimβMLC without important perturbation. The data are discussed in relation to the formation of possible DMPC bicellar aggregates such as those known to occur after insertion of dihexanoylphosphatidylcholine (DHPC). These bicelles are in particular associated with similar deuterium NMR spectra exhibiting identical composite isotropic components which were never characterized before.

A Flexible Aromatic Amphiphilic Trication for the Solubilization of Hydrophobic Organic Semiconductors in Water

Amphiphiles are widely explored for the solubilization of various hydrophobic molecules especially drugs in water. Recently, aromatic amphiphiles emerged as a new class of molecules for the solubilization of hydrophobic organic semiconductors in water. However, the synthesis of these systems involves several steps and often requires the use of expensive metal catalysts. Here we describe the design and synthesis of a new type of flexible aromatic amphiphilic trication (FAT) and its application for solubilization of hydrophobic organic semiconductors in water. FAT has been synthesized in two steps without the use of any expensive metal catalysts. We observed that FAT self-assembles in water into bilayer two-dimensional (2D) nanosheets composed of hydrophobic naphthalimide units. FAT is found to be effective for the solubilization of various hydrophobic organic semiconductors such as perylene, perylene diimide and C60 in water by encapsulating them into its hydrophobic domains. Moreover, FAT was also explored for the solubilization of a 2D conjugated ladder polymer, TQBQ (triquinoxalinylene and benzoquinone), in water.

Hydrogen sulfide detection induced burst release of model drug from polymeric micelles

In this study, a poly(ester-amide)-based amphiphilic polymer (named P1) is prepared for the burst release of a model drug, rhodamine, from polymeric micelles, triggered by hydrogen sulfide (H2S) detection. P1 was synthesized by the Passerini multicomponent polymerization of a hydrophobic H2S-specific unit (M1) with 6-isocyanohexanoic acid, and hydrophilic polyethylene glycol (PEG) dicarboxylic acid. When P1 self-assembles in water, it generates polymeric micelles consisting of a hydrophilic PEG shell and a hydrophobic core derived from M1 with 6-isocyanohexanoic acid. P1 micelles exhibited selective colorimetric (colorless to yellow) and fluorometric (non-emissive to blue emission) H2S detection in water. The limit of detection was as low as 0.09 mM. Upon the exposure of H2S to a P1 micelle solution encapsulating the hydrophobic model drug, rhodamine, H2S detection induced a sequential and self-destructive elimination process of the polymer backbone, resulting in the swelling of the micelles and the abrupt release of rhodamine.

An amphiphilic [2]biphenyl-extended pillar[6]arene: Synthesis, controllable self-assembly in water and application in cell-imaging

Synthesis and functionalization of novel macrocyclic host molecules are important topics in supramolecular chemistry. In this work, the first amphiphilic [2]biphenyl-extended pillar[6]arene (AM-[2]BP-ExP6) was designed and synthesized with poly(ethylene glycol) chains as the hydrophilic tails and a rigid cavity as the hydrophobic core. Due to its amphiphilic nature, AM-[2]BP-ExP6 could self-assemble to stable fibers in water. What's more, AM-[2]BP-ExP6 could associate with quaternary ammonium modified tetraphenylethylene guest (QTPE) to form a 2:1 host-guest complex, accompanied by significant enhanced fluorescence. Interestingly, different like AM-[2]BP-ExP6, AM-[2]BP-ExP6⊃QTPE host-guest complex self-assembled into fluorescent particles with diameter about 310 nm, the obtained fluorescent particles can be further employed in living cell imaging.

Thermosensitive Hydrogels of BAB Triblock Copolymers Exhibiting Gradually Slower Exchange Dynamics and an Unexpected Critical Reorganization Temperature Upon Heating

BAB amphiphilic triblock copolymers comprising poly(methoxyethyl acrylate) (PMEA) B blocks of variable degrees of polymerization (x = 50, 100, or 200) and a central poly(dimethyl acrylamide) (PDMAc) hydrophilic A block with a degree of polymerization y = 400 were synthesized by reversible addition fragmentation chain transfer polymerization, and their self-assembly in water was studied by light scattering and rheology. The BAB triblocks form a transient network in aqueous solution consisting of hydrophobic B cores bridged by hydrophilic A blocks. The exchange of B blocks is fast at low temperature (10 °C) and/or low x values because PMEA is not too hydrophobic. However, the PMEA blocks become more hydrophobic with increasing temperature, leading to a decrease of the exchange rate of the B blocks and to tunable thermo-thickening properties, opposite to the classical Arrhenius behavior. In contrast to many thermosensitive BAB triblocks that undergo an abrupt sol–gel transition above the critical solubility temperature of the B blocks, the hydrophobicity of PMEA gradually increases with T, leading to a progressive increase of the viscosity of the polymer dispersion. In addition, an unprecedented reorganization of the network was observed by rheology at a critical temperature, leading to a further decrease of the exchange rate of the B blocks that is not fully reversible. These features were attributed to the progressive variation of the hydrophobic character and hydration of PMEA with temperature.