Preparation of Thermo- and pH-Responsive Microgels Based on Complementary Nucleobase Molecular Recognition.

Complementary interactions between the natural nucleobases is one of the important ways of biomolecular recognition. Although scientists have introduced such supramolecular noncovalent interactions into biomimetic materials through different approaches in recent years, further research is still needed to confer structural features of biomolecules into emerging stimuli-responsive microgels. In this study, a series of bis-thymine end decorated flexible poly (N-isopropyl acrylamide) (T-PNIPAM-T) are obtained through a thymine esterified RAFT agent. Meanwhile, a rigid polymeric backbone poly[1-(4-vinyl benzyl)] adenine (PS A), including several pendant adenines on the side chain is prepared. Through nucleobase complementary pairing subtle supramolecular cross-linked 3D networks are constructed, and further self-assembled to form microgels under the balance between hydrophilicity and block flexibility. More importantly, such supramolecular 3D microgels show volumetric shrinkage in different water content environments and the assembly behavior under thermo and pH stimulated conditions. This exploration is expected to play an important value and significance in the field of biomimetic controlled release of soft matter in the future.

DIAGNOSTIC PERFORMANCES OF 18F-FLUOROCHOLINE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY AND REPEATED ULTRASONOGRAPHY IN DETECTING UNDEFINED LESIONS IN PATIENTS WITH AN INDICATION FOR PRIMARY HYPERPARATHYROIDISM SURGERY.

Context: 18F-fluorocholine (FCH) has been used as a positron emission tomography (PET) tracer in the localization of hyper-functioning parathyroid glands (HPGs). Objective: We performed this methodological study to evaluate the diagnostic performance of 18F-FCH PET/computerized tomography (CT) and repeated ultrasonography (USG) in detecting unidentified lesions in patients with primary hyperparathyroidism (PHPT). Design: In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and a repeated USG in detecting unidentified parathyroid lesions. Subjects and Methods: Twenty-eight patients who were diagnosed with PHPT, had an indication for surgery following the current guidelines and had no identified lesion on 99mTc-MIBI SPECT/CT, USG, or other imaging methods than 18F-FCH PET/CT, included in the study. Results: While lesions were detected in 26 patients via 18F-FCH PET/CT among 28 patients [92.9% (95% CI: 76.6%-99.1%)], the lesion detection rate was 95.7% (95% CI: 78.1%-99.9%) in 23 patients who underwent a repeated USG. The sensitivity and the accuracy of both 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. Conclusions: This study supports that the combination of 18F-FCH PET/CT and repeated USG has promising potential for being an imaging technique for early detection and localization of HPGs.

Polymer Nanodiscs and Their Bioanalytical Potential.

Membrane proteins (MPs) play a pivotal role in cellular function and are therefore predominant pharmaceutical targets. Although detailed understanding of MP structure and mechanistic activity is invaluable for rational drug design, challenges are associated with the purification and study of MPs. This review delves into the historical developments that became the prelude to currently available membrane mimetic technologies before shining a spotlight on polymer nanodiscs. These are soluble nanosized particles capable of encompassing MPs embedded in a phospholipid ring. The expanding range of reported amphipathic polymer nanodisc materials is presented and discussed in terms of their tolerance to different solution conditions and their nanodisc properties. Finally, the analytical scope of polymer nanodiscs is considered in both the demonstration of basic nanodisc parameters as well as in the elucidation of structures, lipid-protein interactions, and the functional mechanisms of reconstituted membrane proteins. The final emphasis is given to the unique benefits and applications demonstrated for native nanodiscs accessed through a detergent free process.

Bifunctional RAFT Agent Directed Preparation of Polymer/Graphene Oxide Composites.

Polymer/graphene oxide (GO) composites, which combine the physical properties of GO and the processability of polymers, are of increasing interest in a variety of applications ranging from conductive foams, sensors, to bioelectronics. However, the preparation of these composites through physical blending demands the polymers with functional groups that interact strongly with the GO. Here the design and synthesis of a new bifunctional reversible addition-fragmentation chain transfer (RAFT) agent are demonstrated, which allows the synthesis of polymers with predetermined molecular weights and low dispersibilities (Ð), while having functionalities at both polymer termini that allow strong binding to GO. To access polymers with diverse thermal and mechanical properties, acrylonitrile-styrene-acrylate (ASA) copolymers with different types of acrylates, both short and long side chains, are synthesized under the control of the bifunctional RAFT agent. Furthermore, the strong binding between GO and the synthesized polymers is verified and explored to prepare polymer/GO composites with diverse tensile strengths and conductivity in the range of semiconductors. Overall, this novel RAFT agent is expected to expand the utility of polymer/GO composites by providing well-defined polymers with tunable properties and strong binding with GO.

Facile Synthesis of CO2 -Responsive Nano-Objects: Batch versus Semi-Batch RAFT Copolymerization.

Precise polymer architecture and self-assembled morphological control are attractive due to their promising applications, such as drug delivery, biosensors, tissue engineering and "smart" optical systems. Herein, starting from the same hydrophilic units poly(ethylene glycol) (PEG), using CO2 -sensitive monomer N, N-diethylaminoethyl methacrylate (DEAEMA) and hydrophobic monomer benzyl methacrylate (BzMA), a series of well-defined statistical, block, and gradient copolymers is designed and synthesized with similar degree of polymerization but different monomer sequences by batch and semi-batch RAFT polymerization process and their CO2 -responsive behaviors of these nano-objects is systematically studied. The gradient copolymers are generated by using semi-batch methods with programmed monomer feed rate controlled by syringe pumps, achieving precise control over desired gradient copolymer composition distribution. In aqueous solution, the copolymers could self-assemble into various aggregates before CO2 stimulus. Upon bubbling CO2 , the gradient copolymers preferred to form nanosheet-like structures, while the block and statistical copolymers with similar molar mass could only form larger vesicles with thinner membrane thickness or disassemble. The semi-batch strategy to precisely control over the desired composition distribution of the gradient segment presents an emerging trend for the fabrication and application of stimuli-responsive polymers.

Gas-Responsive Self-Assemblies for Mimicking the Alveoli.

In human body, alveoli are the primary sites for gas exchange which are formed by the dilation and protrusion of bronchioles at the end of the lung, and the rapid gas-exchanging process in the alveoli ensures normal life activities. Based on the unique structures and functions of alveoli, it is necessary to study the regulation mechanism of its formation, respiration, and apoptosis. Herein, a class of reversible addition-fragmentation chain transfer (RAFT)-derived amphiphilic triblock copolymers, PEO-b-P(DEAEMA-co-FMA)-b-PS is designed and synthesized. Due to the amphiphilic and gas-responsive segments, these triblock copolymers can self-assemble in aqueous solution and undergo the morphological transition from nanotubes to vesicles under gas stimulation; meanwhile, in the cycles of CO2 /O2 stimulation, these vesicles can further realize the volume expansion and contraction, eventually rupture. The gas-driven morphological transformations of these aggregates successfully imitate the formation, respiration, and apoptosis of alveoli, and provide an essential basis for revealing the life phenomena.

Novel Amphiphilic Block Copolymers for the Formation of Stimuli-Responsive Non-Lamellar Lipid Nanoparticles.

Non-lamellar lyotropic liquid crystalline (LLC) lipid nanoparticles contain internal multidimensional nanostructures such as the inverse bicontinuous cubic and the inverse hexagonal mesophases, which can respond to external stimuli and have the potential of controlling drug release. To date, the internal LLC mesophase responsiveness of these lipid nanoparticles is largely achieved by adding ionizable small molecules to the parent lipid such as monoolein (MO), the mixture of which is then dispersed into nanoparticle suspensions by commercially available poly(ethylene oxide)-poly(propylene oxide) block copolymers. In this study, the Reversible Addition-Fragmentation chain Transfer (RAFT) technique was used to synthesize a series of novel amphiphilic block copolymers (ABCs) containing a hydrophilic poly(ethylene glycol) (PEG) block, a hydrophobic block and one or two responsive blocks, i.e., poly(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate) (PTBA) and/or poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). High throughput small angle X-ray scattering studies demonstrated that the synthesized ABCs could simultaneously stabilize a range of LLC MO nanoparticles (vesicles, cubosomes, hexosomes, inverse micelles) and provide internal particle nanostructure responsiveness to changes of hydrogen peroxide (H2O2) concentrations, pH and temperature. It was found that the novel functional ABCs can substitute for the commercial polymer stabilizer and the ionizable additive in the formation of next generation non-lamellar lipid nanoparticles. These novel formulations have the potential to control drug release in the tumor microenvironment with endogenous H2O2 and acidic pH conditions.

Machine learning based temperature prediction of poly(N-isopropylacrylamide)-capped plasmonic nanoparticle solutions.

The temperature-dependent optical properties of gold nanoparticles that are capped with the thermo-sensitive polymer: 'poly(N-isopropylacrylamide)' (PNIPAM), have been studied extensively for several years. Also, their suitability to function as nanoscopic thermometers for bio-sensing applications has been suggested numerous times. In an attempt to establish this, many have studied the temperature-dependent optical resonance characteristics of these particles; however, developing a simple mathematical relationship between the optical measurements and the solution temperature remains an open challenge. In this paper, we attempt to systematically address this problem using machine learning techniques to quickly and accurately predict the solution-temperature, based on spectroscopic data. Our emphasis is on establishing a simple and practically useful solution to this problem. Our dataset comprises spectroscopic absorption data from both nanorods and nanobipyramids capped with PNIPAM, measured at discretely varied and pre-set temperature states. Specific regions of the spectroscopic data are selected as features for prediction using random forest (RF), gradient boosting (GB) and adaptive boosting (AB) regression techniques. Our prediction results indicate that RF and GB techniques can be used successfully to predict solution temperatures instantly to within 1 °C of accuracy.

Polymer Synthesis with More Than One Form of Living Polymerization Method.

Controlled radical polymerization (CRP) or controlled/living radical polymerization has revolutionized the polymer industry as a tool for the preparation of a wide variety of polymers. This process enables the preparation of polymers with good control of molecular weight, narrow polydispersity, and a range of architectures including block and graft copolymers, star polymers, and other functional polymers. The mechanistic transformation reaction provides a great opportunity to tune chemical and physical properties of copolymers. It can be applied to combine different homopolymers using post-modification techniques or by the use of a dual initiator, allowing the combination of mechanistically distinct polymerization reactions. This review will cover CRP transformations including the synthesis of block copolymers with both linear structures (AB, ABA, (AB) n , multiblocks, etc.) and branched macromolecular architectures (graft, miktoarm star, and dendritic-like), which are obtained by a combination of more than one form of living polymerization reaction.

Glycosylated Reversible Addition-Fragmentation Chain Transfer Polymers with Varying Polyethylene Glycol Linkers Produce Different Short Interfering RNA Uptake, Gene Silencing, and Toxicity Profiles.

Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work, we report the design, synthesis, and biological evaluation of a novel polymeric delivery vector incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of carbohydrate functionality and its distance from the polymer backbone is conducted using reversible addition-fragmentation chain transfer polymerization and postpolymerization modification.

Comparing Gene Silencing and Physiochemical Properties in siRNA Bound Cationic Star-Polymer Complexes.

The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition-Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness, and surface charge of the complexes with and without the protein corona. This is one of the first examples of a comprehensive physiochemical analysis of siRNA-polymer complexes being performed alongside in vitro biological assays, allowing us to describe a set of desirable physical features of cationic polymer complexes that promote gene silencing. Multifaceted studies such as this will improve our understanding of structure-function relationships in nanotherapeutics, facilitating the rational design of polymer-mediated siRNA delivery systems for novel treatment strategies.

Biochemical analysis of the living human vitreous.

BACKGROUND: To date, our understanding of the biochemical composition of the living human vitreous relies on extrapolations from animal or human post-mortem studies. METHODS: This was a cross-sectional study of vitreous samples from 27 individuals scheduled for retinal surgery within a tertiary hospital. From each vitreous sample, the concentrations of sodium, potassium, chloride, calcium, magnesium, glucose, lactate, ß- hydroxybutyrate, copper, zinc, selenium, iron, ferritin and transferrin and osmolality were measured. Perioperative serum samples were also obtained for comparison. RESULTS: The following vitreous mean ± standard deviation (95% confidence interval of the mean) was observed for each analyte: sodium, 146.7 ± 3.3 (145.4-148.0) mmol/L; potassium, 5.73 ± 0.86 (5.39-6.08) mmol/L; chloride, 121.6 ± 2.6 (120.6-122.7) mmol/L; calcium, 1.128 ± 0.518 (0.923-1.333) mmol/L; magnesium, 0.900 ± 0.158 (0.838-0.962) mmol/L; glucose, 2.97 ± 0.98 (2.58-3.36) mmol/L; lactate, 3.97 ± 1.09 (3.54-4.40) mmol/L; osmolality, 289.5 ± 6.9 (286.6-292.5) mOsm/kg; BOHB, 0.0937 ± 0.0472 (0.0750-0.1124) mmol/L; copper, 0.519 ± 0.269 (0.412-0.625) µmol/L; zinc, 1.95 ± 1.09 (1.52-2.38) µmol/L; selenium, 0.1035 ± 0.0276 (0.0923-0.1146) µmol/L; iron, 3.11 ± 1.40 (2.56-3.66) µmol/L; ferritin, 19.5 ± 10.3 (15.5-23.6) µg/L; transferrin, 0.0878 ± 0.0526 (0.0670-0.1086) g/L. Vitreous biochemistry was not significantly different between male and female participants. Vitreous biochemistry was significantly different between non-diabetic and diabetic participants. Vitreous biochemistry was significantly different from the vitreous substitute BSS Plus (Alcon, USA). The vitreous extracted from living humans was markedly different from the commonly reported reference values obtained from animal studies. CONCLUSIONS: The current data provide hitherto unavailable information about the biochemical composition of the living human vitreous.

An arm-first approach to cleavable mikto-arm star polymers by RAFT polymerization.

Redox-cleavable mikto-arm star polymers are prepared by an "arm-first" approach involving copolymerization of a dimethacrylate mediated by a mixture of macroRAFT agents. Thus, RAFT copolymerization of the monomers BMA, DMAEMA, and OEGMA, with the disulfide dimethacrylate cross-linker (DSDMA), bis(2-methacryloyl)oxyethyl disulfide, mediated by a 1:1:1 mixture of three macroRAFT agents with markedly different properties [hydrophilic, poly[oligo(ethylene glycol) methacrylate]-P(OEGMA)8-9 ; cationizable, poly[2-(dimethylamino)ethyl methacrylate]-P(DMAEMA); hydrophobic, poly(n-butyl methacrylate)-P(BMA)] provides low dispersity mikto-arm star polymers. Good control (D < 1.3) is observed for the target P(DMAEMA)/P(OEGMA)/P(BMA) (3:3:1) mikto-arm star, a double hydrophilic P(DMAEMA)/P(OEGMA) (3:3) mikto-arm star and a hydrophobic P(BMA) homo-arm star. However, D for the target mikto-arm stars increases with an increase in either the ratio [DSDMA]:[total macroRAFT] or the fraction of hydrophobic P(BMA) macroRAFT agent. The quaternized mikto-arm star in dilute aqueous solution shows a monomodal particle size distribution and an average size of ≈145 nm.

Carbon Dioxide Capture by Emerging Innovative Polymers: Status and Perspectives.

A significant amount of research has been conducted in carbon dioxide (CO2) capture, particularly over the past decade, and continues to evolve. This review presents the most recent advancements in synthetic methodologies and CO2 capture capabilities of diverse polymer-based substances, which includes the amine-based polymers, porous organic polymers, and polymeric membranes, covering publications in the last 5 years (2019-2024). It aims to assist researchers with new insights and approaches to develop innovative polymer-based materials with improved capturing CO2 capacity, efficiency, sustainability, and cost-effective, thereby addressing the current obstacles in carbon capture and storage to sooner meeting the net-zero CO2 emission target.

Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.

Clinical behaviour of papillary thyroid cancer oncocytic variant: stage-matched comparison versus classical and tall cell variant papillary thyroid cancer.

OBJECTIVE: Papillary thyroid cancer (PTC) has many variants and most of them are mild tumors. Oncocytic variant (OV) is a rare subtype of PTC. There are controversial results about its prognosis in the literature. We investigated its aggressivity and clinical course by comparing it with classical variant (CV) and tall cell variant (TV) of PTC over a stage-matched design. MATERIAL AND METHODS: Pure 100 OV, 71TV and 1219 CV were included in this retrospective cohort study. OV was compared with CV and TV according to independent prognostic parameters. OV was also compared stage by stage with CV and TV for recurrence. RESULTS: Mean age was 46,8 years and male/female ratio 25/75 for OV. The recurrence rates in our study were 16% in OV, 13,5% in CV and 56% in TV. There is a statistically significant difference according to recurrence between stage I and stage IV OV and CV (p=0.023, p=0.03, respectively). There is also a statistically significant difference between stage I and stage IV OV and TV according to recurrence (p=0.001, p=0.024, respectively). OV can be supposed to behave between CV and TV, but very closer to CV. CONCLUSIONS: OV seems to be slightly more aggressive than CV. Despite an inadequate sample size for stage II and III, our findings imply an increased recurrence risk for OV than CV at the advanced stages (stage III and IV) and CV has an unfavorable prognosis than OV at early stages (stage I and II) according to stage-matched model.

Star-Shaped Thermoplastic Elastomers Prepared via RAFT Polymerization.

Styrene-based thermoplastic elastomers (TPEs) demonstrate excellent overall performance and account for the largest industrial output. The traditional methods of preparation styrene-based thermoplastic elastomers mainly focused on anionic polymerization, and strict equipment conditions were required. In recent years, controlled/living radical polymerization (CRP) has developed rapidly, enabling the synthesis of polymers with various complex topologies while controlling their molecular weight. Herein, a series of core crosslinked star-shaped poly(styrene-b-isoprene-b-styrene)s (SISs) was synthesized for the first time via reversible addition-fragmentation chain transfer (RAFT) polymerization. Meanwhile, linear triblock SISs with a similar molecular weight were synthesized as a control. We achieved not only the controlled/living radical polymerization of isoprene but also investigated the factors influencing the star-forming process. By testing the mechanical and thermal properties and characterizing the microscopic fractional phase structure, we found that both the linear and star-shaped SISs possessed good tensile properties and a certain phase separation structure, demonstrating the characteristics of thermoplastic elastomers.

RAFT Polymer-Based Surfactants for Minerals Recovery.

Reagent consumption is an ongoing sustainability challenge for the mineral processing industry. There is a need to recover, regenerate, and reuse as many of the chemical inputs as possible. This study investigated the design and synthesis via reversible addition-fragmentation chain transfer (RAFT) polymerization of a novel polymer for use as a surfactant in a water-in-oil (w/o) emulsion system for ultrafine minerals recovery. The polymers were designed to hold a thermoresponsive moiety to allow for future recovery. The performance of the novel emulsion was tested for agglomeration of ultrafine talc mineral particles. A traditional emulsion containing sorbitan monooleate as the surfactant was used as a research benchmark to compare against the novel emulsion's stability and performance in minerals recovery. The novel RAFT polymer-based emulsions formed large and stable water droplets surrounded by a halo of smaller water droplets. Over time, the smaller droplets coalesced and a more uniform size distribution of droplets was formed, keeping the emulsion stable. Rheological testing of freshly made and aged emulsions showed both traditional and novel emulsions to have a high viscosity at a low shear rate. RAFT polymer B with a hydrophilic-lipophilic block ratio of 5:10 performed adequately as a surfactant replacement to stabilize w/o emulsions. The mineral recovery using the novel emulsion was on par with the traditional emulsions. The novel RAFT emulsion containing 2.5 wt % polymer B achieved 90% minerals recovery, a similar yield to the traditional emulsions. This study demonstrates that surfactants containing stimuli-responsive moieties can be synthesized via RAFT polymerization and successfully used in mineral processing applications to recover ultrafine particles. Work is ongoing to exploit the stimuli responsiveness to recover the polymer surfactant for reuse.

Paclitaxel-loaded cubosome lipid nanocarriers stabilised with pH and hydrogen peroxide-responsive steric stabilisers as drug delivery vehicles.

Responsive nanoparticle delivery systems hold great potential for next-generation chemotherapeutic treatment with reduced off-target side effects. In this work, we formulated responsive lipid-based cubosomes loaded with paclitaxel (PTX) as a model drug and stabilised by novel amphiphilic block copolymers (ABCs) containing the pH-responsive poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and/or the hydrogen peroxide (H2O2)-responsive poly(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate) (PTBA) blocks. The results showed that these cubosomes with a particle size of around 250 nm exhibited excellent PTX encapsulation efficiency of up to 60% and had the ability to control the release rate of the drug in response to pH and H2O2 changes. Specifically, compared to the physiological pH of 7.4, PTX was released faster from the cubosome carriers when exposed to pH 5.5 and/or 50 mM H2O2 conditions, which are pathological conditions found in a tumour microenvironment. In vitro cytotoxicity and cell uptake studies further investigated the cellular interactions of these cubosomes. It was found that cubosomes containing PTX had more toxic effects than the control free PTX sample. Compared to cubosomes stabilised by the non-responsive block copolymer Pluronic® F127, the ABC-stabilised cubosomes also had higher cell internalisation efficiency demonstrated by the cytoplasmic fluorescence intensities using confocal microscopy. These results demonstrated that ABCs containing responsive moieties can stabilise lipid cubosomes and enhance controlled release of poorly soluble chemotherapeutics and cellular uptake.

Membrane interaction and selectivity of novel alternating cationic lipid-nanodisc assembling polymers.

Synthetic polymer nanodiscs are self-assembled structures formed from amphipathic copolymers encapsulating membrane proteins and surrounding phospholipids into water soluble discs. These nanostructures have served as an analytical tool for the detergent free solubilisation and structural study of membrane proteins (MPs) in their native lipid environment. We established the polymer-lipid nanodisc forming ability of a novel class of amphipathic copolymer comprised of an alternating sequence of N-alkyl functionalised maleimide (AlkylM) of systematically varied hydrocarbon chain length, and cationic N-methyl-4-vinyl pyridinium iodide (MVP). Using a combination of physicochemical techniques, the solubilisation efficiency, size, structure and shape of DMPC lipid containing poly(MVP-co-AlkylM) nanodiscs were determined. Lipid solubilisation increased with AlkylM hydrocarbon chain length from methyl (MM), ethyl (EtM), n-propyl (PM), iso-butyl (IBM) through to n-butyl (BM) maleimide bearing polymers. More hydrophobic derivatives formed smaller sized nanodiscs and lipid ordering within poly(MVP-co-AlkylM) nanodiscs was affected by nanodisc size. In dye-release assays, shorter N-alkyl substituted polymers, particularly poly(MVP-co-EtM), exhibited low activities against eukaryotic mimetic POPC membrane and increased their liposome disruption as POPC : POPG membrane mixtures increased in their anionic POPG component, resembling the charge profile of bacterial membranes. These trends in membrane selectivity were transferred towards native cell systems in which gram-positive Staphylococcus aureus and gram-negative Acenobacter baumannii bacterial strains were relatively susceptible to disruption by hydrophobic n-butyl- and n-propyl-poly(MVP-co-AlkylM) derivatives compared to human red blood cells (HRBCs), with a more pronounced selectivity resulting from poly(MVP-co-PM). Such selective membrane interaction by less hydrophobic polymers provides a framework for polymer design towards applications including selective membrane component solubilisation, biosensing and antimicrobial development.