Amphiphilic Polymer Research Articles

Investigation of Amphiphilic PDMS-Hyperbranched Polyglycerol Copolymers to Tune the Fouling-Release Properties in a Moisture Curable Coating System.

Hyperbranched polyglycerol (HBPG) has been proven to be effective as a hydrophilic material when incorporated into amphiphilic copolymers, enhancing fouling-release properties. These amphiphilic polymers not only increase the effectiveness of coatings across a wide range of organisms but also impart antifouling characteristics without resorting to toxic chemicals. HBPGs exhibit high resistance to proteins and lead to the effective removal of marine organisms under low impact pressures. To enhance the effectiveness of HBPGs and facilitate polymer stratification onto the coating surface, copolymers with polydimethylsiloxane (PDMS) were synthesized through a ring-opening multibranching polymerization reaction. These amphiphilic polymers, with varying molecular weights of the PDMS block and different degrees of branching in the HBPG blocks, were incorporated into a urea-siloxane moisture-cure coating system at a concentration of 5 wt %. This study aimed to identify the optimal molecular weight of PDMS and the degree of branching in HBPG that provides the most improved fouling-release (FR) properties to the base coating. The amphiphilic copolymers underwent thorough characterization using Fourier transform infrared (FTIR), NMR, and surface tension measurements. Coatings were extensively characterized for their surface properties by using atomic force microscopy (AFM), photoinduced force microscopy (PiFM), X-ray photoelectron spectroscopy (XPS), moisture adsorption measurements, and contact angle measurements. To assess fouling-release and antifouling properties, laboratory biological assays were conducted with five common marine fouling organisms: Navicula incerta, Celluphaga lytica, Ulva linza, Chlorella vulgaris, and Amphibalanus amphitrite. Notably, 1k or 5k PDMS with a polyglycerol branching ratio of 10:1 or 15:1 emerged as the best performers across a diverse array of laboratory biological assays.

Surfactant-Free Stable Aqueous Shortwave Infrared Amphiphilic π-Conjugated Polymer Nanoparticles.

Novel amphiphilic π-conjugated polymer nanoparticles tailored to efficiently absorb in the near-infrared II (NIR-II) region of the electromagnetic spectrum (>1000nm) are presented. To achieve this, it is statistically introduced triethylene glycol substituted bithiophene moieties in various contents into a polymer backbone consisting of alternating thiophene and [1,2,5]thiadiazolo[3,4-g]quinoxaline. Through systematic modifications of monomer ratios, four amphiphilic conjugated polymers are produced. The presence of hydrophilic side chain, like triethylene glycol monomethyl ether, enhanced the polymer's concentration in aqueous media of up to 470%, versus the D-A thiophene and [1,2,5]thiadiazolo[3,4-g]quinoxaline hydrophobic analog polymer, enabling the production of surfactant-free conjugated polymer nanoparticles (CPNs) with higher concentrations (20.3ppm maximum). Subsequently, the impact of this structural fine-tuning on the optical properties of the polymers and their corresponding CPNs are meticulous investigated. In both cases, it is identified the minimum bithiophene content that maintained the absorption spectra above 1000nm at significantly higher concentrations. So, these findings contribute to the extensive prospects of these materials in multiple fields including biomedical and optoelectronic applications.

Synthesis of Amphiphilic Polymer Co‐Networks via the Growth of a Living RAFT Network

Synthesis of Amphiphilic Polymer Co‐Networks via the Growth of a Living RAFT Network

An antigen-capturing and lymph node-targeting nanoparticle for cancer immunotherapy.

Cancer immunotherapy leverages the immune system to combat cancer and has shown promise for many patients. However, its effectiveness is often hampered by an immunosuppressive tumor microenvironment and the low immunogenicity of tumor cells. In this study, we developed an in situ cancer vaccine that integrates chemotherapy and immunotherapy in a single platform. We synthesized two amphiphilic polymers with poly-albumin-binding domains (PABD) that can target the lymph nodes, PABD-PGEA and PABD-PGED. Compared with previous albumin-hijacking strategies utilizing the same albumin-binding domains, PABD-PGEA exhibited approximately six times greater lymph node-targeting ability, demonstrating enhanced antigen-capturing capability. We loaded PABD-PGEA with doxorubicin (DOX), a drug known to induce immunogenic cell death (ICD) in tumor cells, to form DOX@PABD-PGEA nanomicelles. DOX@PABD-PGEA inhibited tumor growth and extended the survival of mice with B16F10 melanoma through chemotherapy and immunotherapy. Notably, DOX@PABD-PGEA prevented tumor recurrence post-surgery by promoting efficient antigen presentation and reversing immunosuppression in the tumor microenvironment. Our findings suggest that DOX@PABD-PGEA, as an antigen-capturing nanoparticle, provides a safe and effective platform for in situ cancer vaccines and improves cancer immunotherapy.

The Preparation of Cyclic Binary Block Polymer Using Bimolecular Homodifunctional Coupling Reaction and Characterization of Its Performance as a Drug Carrier

There is relatively little research on cyclic amphiphilic block polymers, having both hydrophilic and hydrophobic segments placed in the ring and thus resulting in a higher degree of topological restriction, as drug vehicles. Cyclic amphiphilic binary block polymer is synthesized by the click coupling reaction of bimolecular homodifunctional precursors. The results indicate that cyclization between linear polymer precursors is successful if the trace linear by-products generated are ignored, which also suggests that the small molecule bifunctional terminating agent applied in traditional bimolecular homodifunctional ring-closure process can be extended to large molecule. Moreover, the study on the self-assembly behavior of polymers shows that, compared with linear counterparts, the stability and drug loading capacity of micelles based on the resultant cyclic polymer are not significantly improved due to the influence of topological structure and linear impurities. Nevertheless, drug loaded micelles formed by the obtained cyclic polymers still exhibit superior cellular uptake ability. It can be seen that topological effects do play an irreplaceable role in the application performance of polymers. Therefore, the construction and synthesis of cyclic and its derivative polymers with moderate topological confinement and high purity may be a key direction for future exploration of polymer drug delivery carriers.

Synthesis and Characterization of Lipid-Polyzwitterion Diblock Copolymers for Optimizing Micelle Formation to Enhance Anticancer Drug Delivery in 2D and 3D Cell Cultures.

Amphiphilic polymers with distinct polarity differences, known as sharp polarity contrast polymers (SPCPs), have gained much attention for their ability to form micelles with low critical micelle concentrations (CMCs) and potential in anticancer drug delivery. This study addresses the limited research on structure-property relationships of SPCPs by developing various SPCPs and exploring their physicochemical properties and biological applications. Specifically, the superhydrophobic aliphatic palmitoyl (Pal) was coupled to the superhydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) to form Pal-pMPC diblock copolymers. Adjusting the lengths of hydrophilic chains allowed the creation of structures with varying hydrophilic-hydrophobic ratios for micelle formation. Comprehensive evaluations were carried out, including particle size, CMC, chain exchange rates, cellular uptake efficiency, and anticancer effectiveness. Our findings indicate that micelles with optimal hydrophilic-hydrophobic ratios significantly enhanced cellular uptake and cytotoxicity in both two-dimensional (2D) and three-dimensional (3D) tumor models, offering valuable insights for designing SPCPs for anticancer drug delivery.

Sialic Acid-Modified NIR-II Fluorophore with Enhanced Brightness and Photoconversion Capability for Targeted Lymphoma Phototheranostics.

Lymphoma is a malignant cancer characterized by a rapidly increasing incidence, complex etiology, and lack of obvious early symptoms. Efficient theranostics of lymphoma is of great significance in improving patient outcomes, empowering informed decision-making, and driving medical innovation. Herein, we developed a multifunctional nanoplatform for precise optical imaging and therapy of lymphoma based on a new photosensitizer (1-oxo-1H-benzoo[de]anthracene-2,3-dicarbonitrile-triphenylamine (OBADC-TPA)). OBADC-TPA is a donor-acceptor (D-A) molecule characterized by a novel small coplanar and strong electron-withdrawing acceptor skeleton, while the OBADC moiety facilitates strong intramolecular charge transfer. OBADC-TPA-based nanoparticles (NPs) were prepared through encapsulation with an amphiphilic polymer and subsequent modification with sialic acid (SA). Both in vitro and in vivo studies demonstrated that NPs-SA possessed good biocompatibility, effective tumor accumulation, high photoacoustic (PA) contrast, bright second near-infrared (NIR-II) fluorescence emission, and efficient photothermal/photodynamic conversion capabilities, which can serve as a multifunctional nanocomposite for targeted PA/NIR-II fluorescence imaging-guided synergistic type I/II photodynamic and photothermal therapy (PDT/PTT) of lymphoma. This work not only provides a new NIR-II fluorophore with a novel acceptor moiety but also offers a new, accurate, and effective approach for the targeted diagnosis and treatment of lymphoma, holding promising prospects for clinical application.

High-k organic-inorganic hybrid dielectric material for flexible thin-film transistors and printed logic circuits.

A new photopolymerizable organic-inorganic (O-I) hybrid sol-gel material, AUP@SiOx-184, has been synthesized and utilized as a gate dielectric in flexible organic thin-film transistors (OTFTs). The previously reported three-arm alkoxy-functionalized silane amphiphilic polymer has yielded stable O-I hybrid materials comprising uniformly dispersed nanoparticles in the sol state. In this study, a photosensitizer was introduced, facilitating curing effects under ultraviolet light. Photo-crosslinking enhances the stability of hydroxyl radicals within inorganic nanoparticles, thereby minimizing device hysteresis. This approach also contributes to achieving a low leakage current and a high dielectric constant (high-k) while maintaining reduced thickness. Moreover, AUP@SiOx-184 films are amenable to patterning through UV photopolymerization and can be successfully produced using printing techniques. Compared to other materials, they exhibit outstanding flexibility and improved insulating capabilities. Additionally, OTFTs incorporating AUP@SiOx-184 layers demonstrate extremely stable driving features on flexible substrates. Selective printing and specific patterning play crucial roles in the fabrication of logic circuits. This synthesis strategy has resulted in integrated logic devices that have successfully demonstrated their functionality, highlighting its value for producing functional O-I hybrid materials. Utilizing AUP@SiOx-184 as a gate dielectric in OTFTs showcases its potential to advance electronic technologies that are both flexible and high-performing.

Glutathione-scavenging natural-derived ferroptotic nano-amplifiers strengthen tumor therapy through aggravating iron overload and lipid peroxidation.

Nanomedicine-driven ferroptosis has emerged as a promising tumor treatment strategy through delivering exogenous iron and aggravating the lethal accumulation of lipid peroxides (LPO). However, the compensatory mechanisms of ferroptosis defense systems in cancer cells compromise the therapeutic efficacy and lead to potential side effects. Herein, a highly effective ferroptotic nano-amplifier is designed to synergistically promote ferroptosis via increasing intracellular labile iron, exacerbating lipid peroxidation and overcoming the defense system. Briefly, a natural-derived amphiphilic polymer composing of chondroitin sulfate (CS), arachidonic acid (AA) and a redox-sensitive linker, cystamine (CYS) is constructed to self-assemble as a GSH-responsive nanodrug delivery system for loading bioactive ingredient Polyphyllin I (PPI) and ferric ion (Fe3+). This nanodrug (CSAA/Fe@PPI) can scavenge the aberrant intracellular GSH via CYS linker, accompanied with the degradation of CSAA/Fe@PPI and the release of PPI, AA and Fe3+. On one hand, the intracellular labile iron level is significantly elevated due to the exogenous delivery of Fe3+ and PPI-induced ferritinophagy. On the other hand, ROS burst and the supplement of AA initiate and propagate the lipid peroxidation chain reaction. Meanwhile, the depletion of intracellular GSH suppresses the GPX4 activity, further strengthening the lethal accumulation of LPO. Consequently, the ferroptotic antitumor efficacy is remarkably improved by systemically aggravating iron overload and lipid peroxidation. Therefore, our study presents an effective strategy to improve ferroptosis-based anti-cancer treatment through multiple intervention routes.

Amphiphilic polymer modification of graphene oxide (AGO) to enhance the barrier and corrosion protection properties of waterborne polyurethane coatings

Amphiphilic polymer modification of graphene oxide (AGO) to enhance the barrier and corrosion protection properties of waterborne polyurethane coatings

Chemical structure of lipoteichoic acid in the probiotic strain Latilactobacillus curvatus CP2998.

Latilactobacillus curvatus, found in various fermented foods, is a promising probiotic with unique health benefits. Lipoteichoic acid (LTA) is a characteristic amphiphilic surface polymer of gram-positive bacteria and exhibits immunomodulatory activities. Despite the structural diversity of LTA among different bacterial species and strains, no information is available on the chemical structure of LTA in L. curvatus. In this study, we aimed to determine the structure of LTA isolated from L. curvatus CP2998. One- and two-dimensional nuclear magnetic resonance spectra of intact LTA revealed that LTA had a glycerolphosphate polymer as a hydrophilic main chain with partial substitutions of α-linked glucose and D-alanine at the hydroxy group at position 2 of the glycerol residue. The anchor glycolipid fraction was obtained by hydrofluoric acid treatment. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry spectrum of the anchor glycolipid revealed that it contained diglucosyldiacylglycerol and diglucosylmonoacylglycerol. Our results suggest that L. curvatus CP2998 possesses a typical type I LTA structure; however, the lactic acid bacteria-specific anchor glycolipid structures, such as tri- or tetra-saccharides and three fatty acid residues, were not identified.

Engineering Acid-Promoted Two-Photon Ratiometric Nanoprobes for Evaluating HClO in Lysosomes and Inflammatory Bowel Disease.

HClO is considered a potential contributing factor and biomarker of inflammatory bowel disease (IBD). Accurate monitoring of lysosomal HClO is important for further developing specific diagnostic and therapeutic schedules for IBD. However, only rare types of fluorescent probes have been reported for detecting HClO in IBD so far. Herein, an acid-promoted two-photon semiconducting polymer dot (Lyso-RS Pdot) with dual emission in green and red channels and dual-sensing sites is successfully fabricated with two newly designed polymers NADE-PSMA and PFNA-10TBT as precursors. The red conjugated polymer PFNA-10TBT with pH-inert and HClO-sensitive units is employed to evaluate the HClO concentration in turn-off fluorescence. Meanwhile, the amphiphilic green fluorescent polymer NADE-PSMA sensitive to pH and HClO is employed to evaluate the pH value or HClO concentration in turn-on fluorescence. The resultant Lyso-RS Pdots not only display satisfactory performances for detecting HClO and pH but also achieve accurate two-photon imaging of HClO in lysosomes and the colon of IBD mice based on the distinguished properties such as ratiometric signal output, acid-promoted signal amplification, ultrafast response, and two-photon excitation. The results demonstrate that the HClO level in IBD mice is elevated, and the fast early diagnosis of IBD can be achieved through fluorescence imaging by the proposed Lyso-RS Pdots. This work may provide some solid perspectives for fluorescent diagnosis of H+ and HClO-related diseases.

Triple-action cancer therapy using laser-activated NO-releasing metallomicellar nanophotosensitizer for pyroptosis-driven immune reprogramming.

Cancer photoimmunotherapy represents an intelligent and highly efficient therapeutic approach that harnesses the photothermal effect to precisely target and ablate tumor tissues, while simultaneously modulating the immune system to achieve tumor elimination. The integration of multifunctional therapeutic modalities for combined photoimmunotherapy requires advanced drug delivery systems. However, the design of a single nanoagent capable of serving as a multifunctional nanophotosensitizer remains a significant challenge. In this study, we developed a metallomicellar nanophotosensitizer named TAGNO, which offers a synergistic tri-modal cancer treatment strategy by combining photothermal therapy (PTT), gas therapy (GT), and immunotherapy. The TAGNO nanophotosensitizer consists of a gold nanorod core, responsible for inducing the photothermal effect, coated with an amphiphilic polymer functionalized with tumor cell penetrating peptide to accommodate lipophilic small molecule BNN6, a nitric oxide (NO) donor for GT. We demonstrated that TAGNO exhibited high tumor accumulation, excellent stability, and biocompatibility, ensuring the safe delivery of NO to the tumor site. Upon near-infrared (NIR) laser irradiation, TAGNO effectively raised the temperature within tumor tissues while sparing the surrounding healthy tissues and enabled controlled NO release. Once released, the NO interacts with hydrogen peroxide in the hypoxic tumor microenvironment, forming peroxynitrite (ONOO-), which induces mitochondrial dysfunction and triggers pyroptotic cell death. Pyroptosis induced immunogenic cell death and the subsequent release of tumor antigens, activating cytotoxic T cells and promoting M1 macrophage polarization, effectively controlling both primary and secondary tumor growth. Furthermore, laser-induced NO release facilitated the relaxation of stiff tumor tissues, enhancing blood vessel dilation and oxygenation. This improvement promoted immune cell infiltration while suppressing immunosuppressive cells. Overall, this innovative combination of PTT, GT, and immunotherapy presents a potent and synergistic strategy for the treatment of malignant colon tumors, achieving complete tumor eradication.

Assembly-controlled supramolecular aggregation-induced emission systems based on amphiphilic block polymer hosts

A series of adjustable amphiphilic block polymer hosts with pillar[5]arene units were precisely designed via controlled radical polymerization. Well-defined supramolecular vesicles and/or micelles were constructed with enhanced optical performance.

Development of Tumor-targeting Drug Delivery Systems Based on an Understanding of Polymer Characteristics and the Tumor-specific Environment

Tumor-specific active drug release from macromolecular antitumor drugs after tumor delivery is critical to achieve efficient cellular uptake of the active drug, thereby ensuring therapeutic efficacy. Upon reaching the tumor tissue, protease-facilitated depegylation of pegylated zinc protoporphyrin with ester bonds between PEG and ZnPP (esPEG-ZnPP) occurs, leading to a faster cellular uptake and superior antitumor efficacy compared to PEG-ZnPP with ether bonds (etPEG-ZnPP). This finding provides a viable strategy for achieving efficient tumor-specific drug release by utilizing an ester linkage between PEG and antitumor drugs. Another strategy involves using styrene-maleic acid copolymer (SMA), an amphiphilic polymer. Drug-encapsulating SMA aggregates disintegrate upon interaction with cell membrane components, releasing the encapsulated active drug. The author has demonstrated an improvement in the tumor accumulation of SMA-based macromolecular drugs by conjugating pirarubicin (THP), an anthracycline antitumor drug, with SMA. Furthermore, by conjugating various molecular weights of N-(2-hydroxypropyl)methacrylamide (HPMA) to THP via a hydrazone bond (P-THP, DP-THP, and SP-THP), the author has established a positive correlation between HPMA molecular weight and therapeutic efficacy as well as toxicity. Notably, P-THPs release THP under acidic conditions within tumor tissue; however, this release occurs solely outside tumor cells due to HPMA-mediated inhibition of cellular uptake. The author is currently developing macromolecular anticancer drugs using albumin for the tumor-targeted release of anticancer agents both intra- and extracellularly. The strategic development of tumor-targeting macromolecular antitumor drugs based on a comprehensive understanding of polymer characteristics and the tumor-specific environment is imperative for effective cancer therapy.

Facile construction of polyoxometalate-polymer hybrid nanoparticles with pH/redox dual-responsiveness.

Responsive nanomaterials have emerged as promising candidates for advanced drug delivery systems (DDSs), offering the potential to precisely target disease sites and enhance treatment efficacy. To fulfil their potential, such materials need to be engineered to respond to specific variations in biological conditions. In this work, we present a series of pH/redox dual-responsive hybrid nanoparticles featuring an amphiphilic shell polymer and a pH-responsive core polymer. These nanoparticles incorporate a polyoxometalate (POM), specifically the cobalt(iii)-substituted borotungstate ([BIIIW11O39CoIII]6-), loaded through coordination chemistry between the encapsulated CoIII ions of the POM and pyridyl functional groups on the core polymer. The resulting hybrid nanoparticles show potential for controlled release with excellent stability at physiological pH, and efficient particle disassembly in response to the combination of pH and redox stimuli. Disassembly is proposed to occur following a two step mechanism. Structural rearrangement of the nanoparticle occurs on acidification followed by destabilization of the coordination bond between the polyanion and the pyridyl functionality in the core polymer following reduction. In this system, the POM acts in a novel role as a redox active structural cross-linker. These hybrid dual-responsive nanoparticles, featuring superior colloidal stability under extracellular conditions and controllable disintegration in response to the dual stimuli of acidic pH and redox conditions, provide a novel platform for the controlled intracellular release of therapeutics.

Zwitterionic polymers with high serum tolerance for intracellular protein delivery.

Cationic polymers have been widely developed as carriers for intracellular protein delivery, but face tough challenges such as poor serum tolerance and inevitable material toxicity. Here, we present a type of phase-separating polymer with an anionic surface to address the above issues. A cationic dendrimer is first modified with a hydrophobic moiety to obtain a pH-responsive amphiphilic polymer, which is further conjugated with anionic benzenesulphonate at different grafting degrees. The benzenesulphonate modification facilely changes the hydrophobicity of the polymer and reduces the material cytotoxicity. Interestingly, the polymer can co-assemble with cargo proteins to form nanovesicles for intracellular protein delivery. The benzenesulphonate on the polymer surface bolsters the resistance of polymers to serum proteins, allowing the materials to maintain high delivery efficacy in culture media containing abundant serum proteins. This study provides a facile strategy to design materials with high serum tolerance for intracellular protein delivery.

Modeling and experimental Survey on inverse emulsion terpolymerization of Acrylamide, styrene and maleic anhydride as associative amphiphilic polymer

Modeling and experimental Survey on inverse emulsion terpolymerization of Acrylamide, styrene and maleic anhydride as associative amphiphilic polymer

Core-shell vector-mediated co-delivery of CRISPR/Cas9 system and hydrophobic drugs against triple-negative breast cancer stem cells.

Cancer stem cells (CSCs) play an important role in the development of triple-negative breast cancer (TNBC), including metastasis, invasion, tumorigenicity, and drug resistance. Moreover, non-CSCs can spontaneously transform into CSCs in special tumor microenvironments, thereby leading to poor prognosis or even failed treatments. Therefore, reversing tumor stem cells into normal tumor cells in a sustained-acting manner is a promising strategy. It has been reported that down-regulation of FBXO44 protein expression inhibits tumor cell stemness. Moreover, CRISPR/Cas9 technology, a well-known precise gene editing tool, was adopted to permanently block FBXO44 within the genome upon its successful implementation. Given this, a core-shell nanoparticle (NP) consisting of amphiphilic polymers core and crosslinked-hyaluronic acid shell (nDOX-PL/pFBXO44 NPs) is developed in this work to concurrently deliver FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and doxorubicin (DOX) for combinational CSC reprogramming and chemotherapy of TNBC, which exhibits tumor cell targeting, endosomal escape, and reduction responsiveness to release DOX and plasmids in the cytoplasma. CRISPR/Cas9-mediated downregulation of FBXO44 expression could convert CSC into normal tumor cells, and effectively inhibit tumor growth without obvious side effects in vivo after combining with chemotherapy. In summary, we developed an intelligent system to co-deliver genetic and hydrophobic drugs, achieving effective cancer stemness reversal and synergistic suppression of contractable TNBC.

Tunable Terpolymer Series for the Systematic Investigation of Membrane Proteins.

Membrane proteins (MPs) are critical to cellular processes and serve as essential therapeutic targets. However, their isolation and characterization are often impeded by traditional detergent-based methods, which can compromise their native states, and retention of their native lipid environment. Amphiphilic polymers have emerged as effective alternatives, enabling the formation of nanoscale discs that preserve MPs' structural and functional integrity. We introduce a novel series of poly(styrene-co-maleic acid-co-(N-benzyl)maleimide) (BzAM) terpolymers with tunable amphiphilicity, synthesized through controlled polymerization. Designed to mimic and improve upon industry-standard poly(styrene-co-maleic acid), these well-defined terpolymers offer enhanced control over molecular weight and distribution, allowing for systematic evaluation of polymer properties and their effect on membrane solubilization. The BzAM series effectively solubilized membranes and demonstrated a direct correlation between polymer hydrophobicity and solubilization efficiency of bacterial ABC transporter, Sav1866. This research highlights the importance of rational polymer design in MP research and provides a foundation for future developments.