A Versatile and Robust Vesicle Based on a Photocleavable Surfactant for Two‐Photon‐Tuned Release

A small amphiphile that contains a coumarin unit and alkynyl groups, as a two‐photon‐cleavable segment and polymerizable groups, respectively, was designed and synthesized. The amphiphile showed a critical aggregation concentration of about 4.6×10^?5 M and formed a vesicle‐type assembly. The formed vesicles were stabilized by in situ “click” polymerization without altering their morphology. Hydrophobic and hydrophilic guests can be encapsulated within the vesicle membrane and inside the aqueous core of the vesicle, respectively. The loaded guests can be released from the vesicle by using UV or near‐IR stimuli, through splitting up the amphiphilic structure of the amphiphile. Distinguished dose‐controlled photorelease of the polymeric vesicle is achieved with the maintenance of vesicular integrity, which makes the guest release dependent on the amount of cleavage of the amphiphilic structure during irradiation. This study provides a potential strategy for the development of versatile and stable drug‐delivery systems that offer sustained and photo‐triggered release.     

A novel system of self-reproducing giant vesicles

Novel self-reproducing giant vesicles, consisting of a vesicular amphiphile with an imine group in its hydrophobic chain, were constructed. This vesicular amphiphile, the product of a dehydrocondensation reaction between amphiphilic aldehyde and a lipophilic aniline derivative, could be prepared within the giant vesicles. When a protected form of the aldehyde precursor was added to a suspension of giant vesicles containing the lipophilic aniline precursor and a catalyst, dehydrocondensation between the two precursors took place inside the vesicles and produced the same amphiphile as the one which constitutes the original vesicle. The newly formed amphiphiles self-assembled in the inner water pool to form small vesicles, which were eventually extruded through the outer layer of the original vesicle to the bulk water. Accordingly, this kinetic system can be designated as a self-reproducing system of giant vesicles.     

Preparation of vesicles composed of 2-(hexadecyloxy) cinnamic acid and N-[3-(dimethylamino) propyl]-octadecanamide and their photo- and pH-responsive release property

Vesicles composed of N-[3-(dimethylamino) propyl]-octadecanamide (DMAPODA) and 2-(hexadecyloxy) cinnamic acid (HOCA) in an equimolar ratio were prepared by taking advantage of salt bridge formed between the amino group and the carboxylic group. The structure of vesicle was observed on a Transmission electron microscopy (TEM), and the size was determined on a dynamic light scattering equipment. The phase transition of the vesicular membrane was found to be around 35 °C on a differential scanning calorimeter. HOCA of the vesicular membrane was readily dimerized under the irradiation of a UV light (λ?=?254 nm, 6 W). The release degree of rhodamine B from vesicle suspended in distilled water (pH 6.8) was about 70 % in 1 h at 25 °C, and the UV irradiation during the release experiment had little effect on the release degree. However, it had a significant effect when the temperature of release medium was 40 °C. Upon the photodimerization, HOCA would readily change its orientation in the vesicular membrane vesicle at 40 °C, possibly because the vesicular membrane is in a liquid crystalline state at the temperature, which is higher than the phase transition temperature (around 35 °C). In addition, the vesicle released rhodamine B in a pH-dependent manner. The release degrees were the highest at pH 3.0 and the lowest at pH 9.0 among the pH values tested. The salt bridge formed between DMAPODA and HOCA is labile at a strong acidic condition so it would be responsible for the extensive release at pH 3.0.     

Reduction-responsive vesicles composed of dimethylaminopropyl octadecanamide and dithiodipropionic acid

Reduction-responsive vesicle was prepared by salt-bridging N-[3-(dimethylamino)propyl]-octadecanamide (DMAPODA, a cationic amphiphile) using 3,3′-dithiodipropionic acid (DTPA, a disulfide diacid compound). According to the transmission electron micrograph and the fluorescence quenching degree (53.2%), it could be said that vesicles were formed when the DMAPODA to DTPA molar ratio was 2:2. The DMAPODA/DTPA associate was considered to be a building block for vesicle formation because DTPA could electrostatically associate with DMAPODA and help the cationic amphiphile assemble into the vesicle. On a differential scanning calorimetric thermogram, the DMAPODA/DTPA vesicle showed two endothermic peaks at 50.6°C and 63.2°C. The peak found at the lower temperature was possibly due to the solid gel-to-liquid crystal phase transition of the vesicular membrane and the peak found at the higher temperature was considered to be due to the melting of DMAPODA, indicating that unassociated DMAPODA coexisted with DMAPODA/DTPA vesicles. The release of calcein enveloped in the vesicle was promoted by DL-dithiothreitol, possibly because DTPA can be broken by the reducing agent to form mercaptopropionic acids and the vesicle could be disintegrated and/or the vesicular membrane would become defective.     

Stimuli-responsive supramolecular nanocapsules from amphiphilic calixarene assembly

We synthesized tetrameric amphiphilic molecules based on a calixarene building block that self-assembles into a tunable and stable aggregation structure in aqueous solution. The amphiphilic calixarene molecules with a small hydrophilic part were observed to assemble into a vesicular structure that decreases significantly in diameter with only small increases in the hydrophilic chain length. Further increasing the chain length induced the collapse of the vesicles into spherical micelles. Remarkably, the vesicles were also observed to transform into small globular micelles at lower pH, which can be used to trigger the release of the encapsulated hydrophilic guest molecules.     

Macromolecule-to-Amphiphile Conversion Process of a Polyoxometalate-Polymer Hybrid and Assembled Hybrid Vesicles

We report our findings on the macromolecule-to-amphiphile conversion process of a polyoxometalate-polymer hybrid and the assembled hybrid vesicles formed by aggregation of the hybrid amphiphile. The polyoxometalate-polymer hybrid is composed of a polyoxometalate (POM) cluster, which is covered by five tetrabutylammonium (Bu(4) N(+) ) countercations, and a polystyrene (PS) chain. Through a cation-exchange process the Bu(4) N(+) countercations can be replaced by protons to form a hybrid amphiphile composed of a hydrophilic, protonated POM cluster and a hydrophobic PS chain. By implementing a directed one-dimensional diffusion and analyzing the diffusion data, we confirmed that the diffusion of solvated protons rather than macromolecules or aggregates is the key factor controlling the conversion process. Once the giant hybrid amphiphiles were formed, they immediately assembled into kinetically favored vesicular aggregates. During subsequent annealing these vesicular aggregates were transformed into thermodynamically stable vesicular aggregates with a perfect vesicle structure. The success in the preparation of the POM-containing hybrid vesicles provides us with an opportunity of preparing POM-functionalized vesicles.     

CO2-switchable vesicles-network structure transition and drug release property

A series of amphiphilic triblock polymers based on poly(ethylene glycol) (PEG) and two symmetrical poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) blocks was synthesized via the Atom Transfer Radical Polymerization (ATRP) method. Conductivity, pH, and viscosity tests demonstrated the CO₂-switchability jointly; Cryogenic transmission electron microscopy (Cryo-TEM), Dynamic light scattering (DLS) revealed the self-assembly morphology transformation from unilamellar vesicle to network structure when bubbling CO₂. These changes were all attributed to the protonation of tertiary amine groups in PDMAEMA blocks and the mechanism was proved by ^?H NMR. The vesicles have a relatively low release rate of drug; once stimulated by CO₂, the release rate will be accelerated. The polymeric vesicle has the possibility to find potential applications in drug delivery and release domains.     

Membrane dynamics of a myelin-like giant multilamellar vesicle applicable to a self-reproducing system

A real time observation of a myelin-like giant multilamellar vesicle (mGMV) revealed that it divided into relatively small mGMVs when an aqueous solution of an electrolyte was added. Furthermore, the mGMV showed a division process accompanied by the growth of the dividing mGMVs when a bolaamphiphile which was composed of an electrolyte unit and a vesicular amphiphile unit was added. This vesicular system can be regarded as a self-reproduction of mGMV, where the added amphiphile acts as a supplier of both the vesicular amphiphile and the division initiator.     

Macromolecule-to-Amphiphile Conversion Process of a Polyoxometalate–Polymer Hybrid and Assembled Hybrid Vesicles

We report our findings on the macromolecule-to-amphiphile conversion process of a polyoxometalate–polymer hybrid and the assembled hybrid vesicles formed by aggregation of the hybrid amphiphile. The polyoxometalate–polymer hybrid is composed of a polyoxometalate (POM) cluster, which is covered by five tetrabutylammonium (Bu₄N⁺) countercations, and a polystyrene (PS) chain. Through a cation-exchange process the Bu₄N⁺ countercations can be replaced by protons to form a hybrid amphiphile composed of a hydrophilic, protonated POM cluster and a hydrophobic PS chain. By implementing a directed one-dimensional diffusion and analyzing the diffusion data, we confirmed that the diffusion of solvated protons rather than macromolecules or aggregates is the key factor controlling the conversion process. Once the giant hybrid amphiphiles were formed, they immediately assembled into kinetically favored vesicular aggregates. During subsequent annealing these vesicular aggregates were transformed into thermodynamically stable vesicular aggregates with a perfect vesicle structure. The success in the preparation of the POM-containing hybrid vesicles provides us with an opportunity of preparing POM-functionalized vesicles.     

Amphiphilic diarylethene as a photoswitchable probe for imaging living cells

This communication reports a unique example of water-soluble and fluorescent-switchable amphiphilic diarylethene. This compound performs stable vesicle aggregation in water and shows aggregation-dependent emission in its open form. The fluorescence can be effectively switched by alternating between UV and visible light irradiation. This compound thus can stain KB cells for switchable living cell imaging with excellent resistance to fatigue.     

Preparation and characterization of a novel organic-inorganic nanohybrid "cerasome" formed with a liposomal membrane and silicate surface

A novel class of organic-inorganic hybrids, the so-called cerasomes, which have a bilayer vesicular structure and a silicate surface, has been synthesized by combination of sol-gel reaction and self-assembly of organoalkoxysilanes with a molecular structure analogous to lipids. We have synthesized two cerasome-forming organoalkoxysilanes, N-[N-(3-triethoxysilyl)propylsuccinamoyl]dihexadecylamine (1) and N,N-dihexadecyl-N (alpha)-[6-[(3-triethoxysilyl)propyldimethylammonio]hexanoyl]glycinamide bromide (2), and investigated the synthetic conditions of the cerasomes and their structural characteristics. For the proamphiphilic 1, the cerasome was obtained under restricted pH conditions where acid-catalyzed hydrolysis of the triethoxysilyl moiety proceeded without disturbing the vesicle formation. In contrast, the amphiphilic 2, additionally having a hydrophilic quaternary ammonium group, formed stable dispersions of the cerasome in a wide pH range. The hydrolysis behavior of the triethoxysilyl groups was monitored by (1)H NMR spectroscopy. Morphology of the cerasomes having the liposomal vesicular structure was confirmed by TEM observations. Extent of the development of siloxane networks through condensation among the silanol groups on the cerasome surface was evaluated by using MALDI-TOF-MS spectrometry. Formation of oligomers of the cerasome-forming lipids in the vesicle was clearly confirmed. Due to the siloxane network formation, the cerasome showed remarkably high morphological stability compared with a reference liposome, as evaluated by surfactant dissolution measurements.     

The preparation of amphiphilic core‐shell nanospheres by using water‐soluble macrophotoinitiator

The amphiphilic poly(AM‐co‐SA)‐ITXH macrophotoinitiator was synthesized by precipitation photopolymerization under UV irradiation with isopropylthioxanthone (ITX) as free radical photoinitiator. A novel method has been developed to prepare amphiphilic core‐shell polymer nanospheres via photopolymerization of methyl methacrylate (MMA) in aqueous media, with amphiphilic copolymer macrophotoinitiator poly(AM‐co‐SA)‐ITXH. During polymerization, the amphiphilic macroradicals underwent in situ self‐assembly to form polymeric micelles, which promoted the emulsion polymerization of the monomer. Thus, amphiphilic core‐shell nanospheres ranging from 70 to 140 nm in diameter were produced in the absence of surfactant. The conversion of the monomer, number average molecular weights (M_n), and particle size were found to be highly dependent on the macrophotoinitiator and monomer concentration. The macrophotoinitiator and amphiphilic particles were characterized by FTIR, UV‐vis, ¹H NMR, TEM, DSC, and contact angle measurements. The results showed the particles had well‐defined amphiphilic core‐shell structure. This new method is scientifically and technologically significant because it provides a commercially viable route to a wide variety of novel amphiphilic core‐shell nanospheres. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 936–942, 2010     

Photo‐responsive amphiphilic poly(α‐hydroxy acids) with pendent o‐nitrobenzyl ester constructed via copper‐catalyzed azide‐alkyne cycloaddition reaction

Photo‐responsive block copolymer mPEG‐b‐poly(Tyr)‐g‐NB was prepared by introduction of o‐nitrobenzyl ester group into the side chain of amphiphilic poly(ethylene glycol)‐b‐poly(α‐hydroxy acids) (mPEG‐b‐poly(Tyr)) containing pendent alkynyl group via copper‐catalyzed azide‐alkyne cycloaddition reaction. The amphiphilic mPEG‐b‐poly(Tyr) was synthesized via the ring‐opening polymerization of O‐carboxyanhydrides, with monomethoxy poly(ethylene glycol) (mPEG) as macroinitiator. The molecular structure, self‐assembly, and photo‐controlled release of the obtained mPEG‐b‐poly(Tyr)‐g‐NB were thoroughly investigated. mPEG‐b‐poly(Tyr)‐g‐NB could self‐assemble into spherical micelles in water and showed disassembly under UV light irradiation, which was demonstrated by means of UV‐vis spectroscopy, scan electron microscopes, and dynamic light scattering measurement. Fluorescence emission measurements demonstrated that Nile red, encapsulated by micelles, can be released upon UV irradiation. This study provides a convenient way to construct smart poly(α‐hydroxy acids)‐based nanocarriers for controlled release of hydrophobic drugs. Copyright © 2015 John Wiley & Sons, Ltd.     

Optical switching of self-assembly and disassembly of noncovalently connected amphiphiles

A hydrophobic compound, which we name 3C18-Azo, containing an azo head and three 18 C alkyl chains has the capacity to form an amphiphile by capping it with a cyclodextrin (CD) by inclusion complexation. The amphiphilic compound self-assembles into vesicles in water. Optical switching of the assembly and disassembly is realized by alternating visible and UV irradiation, which causes the isomerization of the azo groups, thus affecting their complexation with the CDs.     

Condensation properties of vesicles formed from an amphiphilic N-phosphorylamino acid

Stable unilamellar vesicles were formed in water under appropriate pH from dispersions of N-(O,O-di-n-hexadecyl)phosphorylalanine, an amphiphilic N-phosphorylamino acid. We found that condensation occurred in the vesicle solution after incubated at 40 degrees C, which may contribute to the stability of the vesicular system. Dipeptide derivative in the vesicle solution was identified by electrospray ionization mass spectrometry (ESI-MS), which suggests the peptide formation without any coupling reagents. Hydrogen bond and electrostatic interactions play important roles in the process of vesicle formation, while the suitable orientation and packing of the amphiphilic molecules at the vesicle/water interface together with certain conformational freedom in the vesicular bilayer are considered to be most favorable for the condensation in ordered systems as vesicles.     

Synthesis and characterization of a biodegradable amphiphilic copolymer based on branched poly(ϵ‐caprolactone) and poly(ethylene glycol)

A novel biodegradable amphiphilic copolymer with hydrophobic poly(ε‐caprolactone) branches containing cholic acid moiety and a hydrophilic poly(ethylene glycol) chain was synthesized. The copolymer was characterized by FTIR, ¹H NMR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), polarizing light microscopy (PLM), and wide‐angle X‐ray diffraction (WAXD) analysis. The amphiphilic copolymer could self‐assemble into micelles in an aqueous solution. The critical micelle concentration of the amphiphilic copolymer was determined by fluorescence spectroscopy. A nanoparticle drug delivery system with a regularly spherical shape was prepared with high encapsulation efficiency. The in vitro drug release from the drug‐loaded polymeric nanoparticles was investigated. Because of the branched structure of the hydrophobic part of the copolymer and the relatively fast degradation rate of the copolymer, an improved release behavior was observed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5256–5265, 2007     

Self-assembled vesicles from amphiphilic platinum(II) terpyridyl complex in water

A new cationic amphiphile (1) functionalised with platinum(II) terpyridyl unit was designed and synthesised to realize self-assembly in water. Using UV–vis and emission spectroscopy, scanning electron microscopy, cryogenic transmission electron microscopy, dynamic light scattering and time-correlated single-photon counting technique, we have demonstrated that amphiphile 1 can self-assemble into stable vesicular aggregates upon direct dissolution in water, which is rarely observed in the literature.     

Synthesis, aggregation, and binding behavior of synthetic amphiphilic receptors

Amphiphilic bowl-shaped receptor molecules have been synthesized starting from diphenylglycoluril. Upon dispersion in water, these molecules self-assemble to form vesicles that bind neutral guests and alkali metal ions. In the case of bis(alkylester)-modified receptor compound 4, electron microscopy reveals that an increase in the size of the alkali metal ion (from Na(+) or K(+) to Rb(+) and to Cs(+)) leads to a change in the shape of the aggregates, viz. from vesicles to tubules. Monolayer experiments suggest that this behavior is due to a change in the conformation of this amphiphilic receptor. In water, molecules of 4 have an elongated conformation that changes to a sandwich-like one upon binding of alkali metal ions. Binding studies with vesicles from the bis-ammonium receptors 6 and 9 and the guest 4-(4-nitrophenylazo)resorcinol (Magneson) reveal that below the critical aggregation concentration (CAC) of the amphiphile 1:1 host-guest complexes are formed with high host-guest association constants. Above the CAC, a host-guest ratio of 2:1 was observed that indicates that only the cavities on the outside of the vesicle can be occupied. In the case of the naphthalene walled compound 8 changes in the vesicle structure are induced by the organic guest Magneson.     

Morphological and compositional evolution of polymeric colloidal monolayer during UV irradiation

In this study, we investigated the morphological and compositional evolution polymeric colloidal monolayer during UV irradiation. A PS colloidal monolayer with interparticle bridges was prepared and exposed to the UV light. As a consequence of photochemical reactions containing chain-scission, UV irradiation induced morphological changes in the monolayer surface including changes in the size, shape, and packing structure of PS particles. By manipulating the UV irradiation time, fine tuning of size and shape of the interstice in the monolayer was achieved. In these procedures, the interparticle bridges play an important role. The UV irradiation induced the formation of polar groups in the PS particle surface and thus the particle surface became highly hydrophilic.     

Investigation of pH-responsive properties of polymeric micelles with a core-forming block having pendant cyclic ketal groups

In this study, three kinds of amphiphilic block copolymers, termed MPEG-block-PDMMA, MPEG-block-PCPMA, and MPEG-block-PMPMA, which were composed of one hydrophilic monomethoxy poly(ethylene glycol) (MPEG) block and one hydrophobic polyacrylate block bearing pendant six-member cyclic ketal groups, were synthesized by atom transfer radical polymerization (ATRP). These polymers can disperse in aqueous media to self-assemble into micellar aggregates with a spherical core-shell structure with mean diameter below 300 nm. The stimuli-responsiveness of polymeric micelles from MPEG-block-PDMMA was detected by fluorescence-probe technique at pH 3.5 and 37 °C. The effect of chemical architecture and composition of the polymers on the pH-responsive properties of polymeric micelles was also studied. A combination of pH and temperature to trigger release behavior of these polymeric micelles was discussed by comparing the encapsulated molecule release ability under various pH and temperature conditions and analyzing chemical structural changes of the polymer before and after the triggering.