Imidazolium-Based Main-Chain Copolymers With Alternating Sequences for Broad-Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms.

In response to the escalating challenge of bacterial drug resistance, the imperative to counteract planktonic cell proliferation and eliminate entrenched biofilms underscores the necessity for cationic polymeric antibacterials. However, limited efficacy and cytotoxicity challenge their practical use. Here, novel imidazolium-based main-chain copolymers with imidazolium (PIm+ ) as the cationic component are introduced. By adjusting precursor molecules, hydrophobicity and cationic density of each unit are fine-tuned, resulting in broad-spectrum bactericidal activity against clinically relevant pathogens. PIm+ 1 stands out for its potent antibacterial performance, with a minimum inhibitory concentration of 32 µg mL-1 against Methicillin-resistant Staphylococcus aureus (MRSA), and substantial biofilm reduction in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms. The bactericidal mechanism involves disrupting the outer and cytoplasmic membranes, depolarizing the cytoplasmic membrane, and triggering intracellular reactive oxygen species (ROS) generation. Collectively, this study postulates the potential of imidazolium-based main-chain copolymers, systematically tailored in their sequences, to serve as a promising candidate in combatting drug-resistant bacterial infections.

Biomedical Application of Porphyrin-Based Amphiphiles and Their Self-Assembled Nanomaterials.

Porphyrins have been vastly explored and applied in many cutting-edge fields with plenty of encouraging achievements because of their excellent properties. As important derivatives of porphyrins, porphyrin-based amphiphiles (PBAs) not only maintain the advanced properties of porphyrins (catalysis, imaging, and energy transfer) but also possess self-assembly and encapsulation capability in aqueous solution. Accordingly, PBAs and their self-assembles have had important roles in diagnosing and treating tumors and inflammation lesions in vivo, but not limited to these. In this article, we introduce the research progress of PBAs, including their constitution, structure design strategies, and performances in tumor and inflammation lesion diagnosis and treatments. On that basis, the defects of synthesized PBAs during their application and the possible effective strategies to overcome the limitations are also proposed. Finally, perspectives on PBAs exploration are updated based on our knowledge. We hope this review will bring researchers from various domains insights about PBAs.

Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy.

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T2-weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10-13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. STATEMENT OF SIGNIFICANCE: Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T2 MRI properties (r2 = 152.13 mM-1s-1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.

Fluorinated hydrogel nanoparticles with regulable fluorine contents and T2 relaxation times as 19F MRI contrast agents.

Medical imaging contrast agents that are able to provide detailed biological information have attracted increasing attention. Among the new emerging imaging contrast agents, 19F magnetic resonance imaging contrast agents (19F MRI CAs) are extremely promising for their weak background disturbing signal from the body. However, to prepare 19F MRI CAs with a long T2 relaxation time and excellent biocompatibility in a simple and highly effective strategy is still a challenge. Herein, we report a new type of 19F MRI hydrogel nanocontrast agents (19F MRI HNCAs) synthesized by a surfactant-free emulsion polymerization with commercial fluorinated monomers. The T2 relaxation time of 19F MRI HNCA-1 was found to be 25-40 ms, guaranteeing its good imaging ability in vitro. In addition, according to an investigation into the relationship between the fluorine content and 19F MRI signal intensity, the 19F MRI signal intensity was not only determined by the fluorine content in 19F MRI HNCAs but also by the hydration microenvironment around the fluorine atoms. Moreover, 19F MRI HNCAs demonstrated excellent biocompatibility and imaging capability inside cells. The primary exploration demonstrated that 19F MRI HNCAs as a new type of 19F MRI contrast agent hold potential for imaging lesion sites and tracking cells in vivo by 19F MRI technology.

Seven-layer analysis model of an optical waveguide excitation fluorescence microscopy.

In this paper, an optical waveguide evanescent field fluorescence microscopy is studied. Based on Maxwell's equation, a seven-layer theoretical analysis model is developed for the evaluation of an optical waveguide excitation fluorescence microscopy. The optical waveguide excitation fluorescence microscopy structure is systematically and comprehensively analysed at the wavelengths of 488, 532 and 646 nm for fluorescent dyes. The analysis results provide some useful suggestions, which will be beneficial to the research of an optical waveguide evanescent field fluorescence microscopy.

Recent Research Progress of 19 F Magnetic Resonance Imaging Probes: Principle, Design, and Their Application.

Visualization of biomolecules, cells, and tissues, as well as metabolic processes in vivo is significant for studying the associated biological activities. Fluorine magnetic resonance imaging (19 F MRI) holds potential among various imaging technologies thanks to its negligible background signal and deep tissue penetration in vivo. To achieve detection on the targets with high resolution and accuracy, requirements of high-performance 19 F MRI probes are demanding. An ideal 19 F MRI probe is thought to have, first, fluorine tags with magnetically equivalent 19 F nuclei, second, high fluorine content, third, adequate fluorine nuclei mobility, as well as excellent water solubility or dispersity, but not limited to. This review summarizes the research progresses of 19 F MRI probes and mainly discusses the impacts of structures on in vitro and in vivo imaging performances. Additionally, the applications of 19 F MRI probes in ions sensing, molecular structures analysis, cells tracking, and in vivo diagnosis of disease lesions are also covered in this article. From authors' perspectives, this review is able to provide inspirations for relevant researchers on designing and synthesizing advanced 19 F MRI probes.

Cell-Derived Vesicles with Increased Stability and On-Demand Functionality by Equipping Their Membrane with a Cross-Linkable Copolymer.

Cell-derived vesicles retain the cytoplasm and much of the native cell membrane composition. Therefore, they are attractive for investigations of membrane biophysics, drug delivery systems, and complex molecular factories. However, their fragility and aggregation limit their applications. Here, the mechanical properties and stability of giant plasma membrane vesicles (GPMVs) are enhanced by decorating them with a specifically designed diblock copolymer, cholesteryl-poly[2-aminoethyl methacrylate-b-poly(ethylene glycol) methyl ether acrylate]. When cross-linked, this polymer brush enhances the stability of the GPMVs. Furthermore, the pH-responsiveness of the copolymer layer allows for a controlled cargo loading/release, which may enable various bioapplications. Importantly, the cross-linked-copolymer GPMVs are not cytotoxic and preserve in vitro membrane integrity and functionality. This effective strategy to equip the cell-derived vesicles with stimuli-responsive cross-linkable copolymers is expected to open a new route to the stabilization of natural membrane systems and overcome barriers to biomedical applications.

Degradable Multifunctional Porphyrin-Based Porous Organic Polymer Nanosonosensitizer for Tumor-Specific Sonodynamic, Chemo- and Immunotherapy.

Sonodynamic therapy (SDT) benefiting from its intrinsic merits, such as noninvasiveness and deep tissue penetrability, is receiving increasing considerable attention in reactive oxygen species (ROS)-based tumor treatment. However, current sonosensitizers usually suffer from low tumor lesion accumulation, insufficient ROS generation efficiency under ultrasound, and non-biodegradability, which seriously impede the therapeutic outcomes. Additionally, it is difficult that SDT alone can completely eradicate tumors because of the complex and immunosuppressive tumor microenvironment (TME). Herein, we simultaneously employ sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds to construct a novel degradable multifunctional porphyrin-based hollow porous organic polymer (POP) nanosonosensitizer (H-Pys-HA@M/R), which combine SDT, "on-demand" chemotherapy, and immunotherapy. Taking the unique advantages of POPs with designable structures and high specific surface area, this H-Pys-HA@M/R nanosonosensitizer can achieve tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activating ROS generation with encouraging results. Furthermore, this multifunctional nanosonosensitizer can effectively evoke immunogenic cell death (ICD) response through the combination of SDT and chemotherapy for both primary and distal tumor growth suppression. Meanwhile, H-Pys-HA@M/R exhibits favorable biodegradation and biosafety. Therefore, this study provides a new strategy for reasonably designing and constructing POP-related sonosensitizers combining SDT/chemotherapy/immunotherapy triple treatment modalities to eradicate malignant tumors.

Imitation-mussel fluorescent silicon quantum dots for selective labeling and imaging of bacteria and biofilms.

Selective labeling of distinct bacteria and biofilm is poised for the fundamental understanding of bacterial activities, interactions, and coupled phenomena occurring at the microscale. However, a simple and effective way to achieve selective bacterial labeling is still lacking. Herein, we report a fluorescence probe with core-shell nanostructure that has polydopamine (PDA) coating on the surface of fluorescent silicon quantum dots (SiQDs@PDA). The surface of the SiQDs@PDA can be functionalized by various molecules (2-mercaptoethylamine hydrochloride, PEG, d-alanine, glucose amide) through different strategies (Michael addition, π-π interaction, and ion-ion interaction). Importantly, the d-alanine (D-Ala)- and gluconamide (Glc)-functionalized SiQDs@PDA fluorescence probes are capable of selectively labeling gram-positive and gram-negative bacteria, as well as their biofilms. The excellent performance in universal functionalization and selective labeling and imaging of bacteria and their biofilms demonstrate that SiQDs@PDA are a promising fluorescence tool in microbe research.

Lipid Perfluorohexane Nanoemulsion Hybrid for MRI-Guided High-Intensity Focused Ultrasound Therapy of Tumors.

Magnetic resonance imaging-guided high-intensity focused ultrasound (MRI-guided HIFU) is a non-invasive strategy of diagnosis and treatment that is applicable in tumor ablation. Here, we prepared a multifunctional nanotheranostic agent (SSPN) by loading perfluorohexane (PFH) and superparamagnetic iron oxides (SPIOs) in silica lipid for MRI-guided HIFU ablation of tumors. PFH was introduced to improve the ablation effect of HIFU and the ultrasound (US) contrast performance. Due to its liquid-to-gas transition characteristic, it is sensitive to temperature. SPIOs were used as an MRI contrast agent. Silica lipid was selected because it is a more stable carrier material compared with normal lipid. Previous studies have shown that SSPNs have good biocompatibility, stability, imaging, and therapeutic effects. Therefore, this system is expected to develop an important therapeutic agent for MRI-guided HIFU therapy against tumors.

Non-coplanar misalignment optical waveguide cantilever sensor with a monotonic response in a large operation range.

This paper reports a non-coplanar misalignment optical waveguide cantilever sensor realizing a monotonic response with a large operation range. A 1×2 Y-branch optical power splitter cantilever structure was designed, and one of the branches was reduced in thickness at the end, as a non-coplanar structure with respect to another. The misalignment coupling of the two branches due to the thickness of one branch leads to a monotonic response of an optical waveguide cantilever sensor. The simulation results showed a monotonic response with a sensitivity of 6×10-4 n m -1 in a large operation range of -1 to 1 µm.

Clustering of catalytic nanocompartments for enhancing an extracellular non-native cascade reaction.

Compartmentalization is fundamental in nature, where the spatial segregation of biochemical reactions within and between cells ensures optimal conditions for the regulation of cascade reactions. While the distance between compartments or their interaction are essential parameters supporting the efficiency of bio-reactions, so far they have not been exploited to regulate cascade reactions between bioinspired catalytic nanocompartments. Here, we generate individual catalytic nanocompartments (CNCs) by encapsulating within polymersomes or attaching to their surface enzymes involved in a cascade reaction and then, tether the polymersomes together into clusters. By conjugating complementary DNA strands to the polymersomes' surface, DNA hybridization drove the clusterization process of enzyme-loaded polymersomes and controlled the distance between the respective catalytic nanocompartments. Owing to the close proximity of CNCs within clusters and the overall stability of the cluster architecture, the cascade reaction between spatially segregated enzymes was significantly more efficient than when the catalytic nanocompartments were not linked together by DNA duplexes. Additionally, residual DNA single strands that were not engaged in clustering, allowed for an interaction of the clusters with the cell surface as evidenced by A549 cells, where clusters decorating the surface endowed the cells with a non-native enzymatic cascade. The self-organization into clusters of catalytic nanocompartments confining different enzymes of a cascade reaction allows for a distance control of the reaction spaces which opens new avenues for highly efficient applications in domains such as catalysis or nanomedicine.

Artificial Melanogenesis by Confining Melanin/Polydopamine Production inside Polymersomes.

Melanin and polydopamine are potent biopolymers for the development of biomedical nanosystems. However, applications of melanin or polydopamine-based nanoparticles are limited by drawbacks related to a compromised colloidal stability over long time periods and associated cytotoxicity. To overcome these hurdles, a novel strategy is proposed that mimics the confinement of natural melanin in melanosomes. Melanosome mimics are developed by co-encapsulating the melanin/polydopamine precursors L-DOPA/dopamine with melanogenic enzyme Tyrosinase within polymersomes. The conditions of polymersome formation are optimized to obtain melanin/polydopamine polymerization within the cavity of the polymersomes. Similar to native melanosomes, polymersomes containing melanin/polydopamine show long-term colloidal stability, cell-compatibility, and potential for cell photoprotection. This novel kind of artificial melanogenesis is expected to inspire new applications of the confined melanin/polydopamine biopolymers.

Research on Claw Motion Characteristics and Cavitation Bubbles of Snapping Shrimp.

Snapping shrimp produces a high-speed jet through the rapid closure of the snapper claw, which stimulates the formation of cavitation bubbles of various shapes. In order to explore the fast motion characteristics of snapper claw, the formation and change process of cavitation, and the physical principles underlying the biological phenomena, the equivalent model of snapper claw was constructed through CT scanning technology. A high-speed camera was used to capture the claw's motion characteristics, thereby simulating the production of cavitation bubbles by snapping shrimp. The results show that the rotation speeds of different species of snapping shrimps are different, as well as their motion characteristics. Cavitation is formed by the interaction of the pressure drop caused by the vortex at the nozzle with the inertia of the liquid inside the socket. Under the influence of the jet, the shapes of bubbles change from ring to cone, and eventually collapse into bubble clouds.

DNA-directed arrangement of soft synthetic compartments and their behavior in vitro and in vivo.

DNA has been widely used as a key tether to promote self-organization of super-assemblies with emergent properties. However, control of this process is still challenging for compartment assemblies and to date the resulting assemblies have unstable membranes precluding in vitro and in vivo testing. Here we present our approach to overcome these limitations, by manipulating molecular factors such as compartment membrane composition and DNA surface density, thereby controlling the size and stability of the resulting DNA-linked compartment clusters. The soft, flexible character of the polymer membrane and low number of ssDNA remaining exposed after cluster formation determine the interaction of these clusters with the cell surface. These clusters exhibit in vivo stability and lack of toxicity in a zebrafish model. To display the breadth of therapeutic applications attainable with our system, we encapsulated the medically established enzyme laccase within the inner compartment and demonstrated its activity within the clustered compartments. Most importantly, these clusters can interact selectively with different cell lines, opening a new strategy to modify and expand cellular functions by attaching such pre-organized soft DNA-mediated compartment clusters on cell surfaces for cell engineering or therapeutic applications.

Segregated Nanocompartments Containing Therapeutic Enzymes and Imaging Compounds within DNA-Zipped Polymersome Clusters for Advanced Nanotheranostic Platform.

Nanotheranostics is an emerging field that brings together nanoscale-engineered materials with biological systems providing a combination of therapeutic and diagnostic strategies. However, current theranostic nanoplatforms have serious limitations, mainly due to a mismatch between the physical properties of the selected nanomaterials and their functionalization ease, loading ability, or overall compatibility with bioactive molecules. Herein, a nanotheranostic system is proposed based on nanocompartment clusters composed of two different polymersomes linked together by DNA. Careful design and procedure optimization result in clusters segregating the therapeutic enzyme human Dopa decarboxylase (DDC) and fluorescent probes for the detection unit in distinct but colocalized nanocompartments. The diagnostic compartment provides a twofold function: trackability via dye loading as the imaging component and the ability to attach the cluster construct to the surface of cells. The therapeutic compartment, loaded with active DDC, triggers the cellular expression of a secreted reporter enzyme via production of dopamine and activation of dopaminergic receptors implicated in atherosclerosis. This two-compartment nanotheranostic platform is expected to provide the basis of a new treatment strategy for atherosclerosis, to expand versatility and diversify the types of utilizable active molecules, and thus by extension expand the breadth of attainable applications.

Aptamer-Functionalized Gold Nanostars for on-Demand Delivery of Anticancer Therapeutics.

Gold nanostars (AuNS) are promising carriers for targeted delivery of therapeutic oligonucleotides, but their potential in fabricating an on-demand drug release system in a facile and robust way remains to be explored. In this paper, we used a model aptamer (HApt), acting not only as a target ligand but also as a natural thermal-responsive material, to decorate AuNS. The prepared gold nanoconstruct, HApt@AuNS, displayed stoichiometric loading capacity of the anthracycline drug doxorubicin (Dox). The on-demand drug release was realized by illuminating nanoconstructs with near-infrared (NIR) light. Furthermore, a higher degree of Dox release from the nanoconstructs was achieved in an acidic environment, compared to neutral conditions. The in vitro experiments showed that Dox-intercalation did not affect the cell uptake efficiency of HApt@AuNS, which could enter cells through clathrin-mediated endocytosis and microtubule-dependent active transport to lysosomes. Dox-loaded HApt@AuNS exhibited intracellular on-demand drug release and enhanced toxicity against cancer cells by NIR-irradiation.

Brushing the surface: cascade reactions between immobilized nanoreactors.

Functionalization of hard or soft surfaces with, for example, ligands, enzymes or proteins, is an effective and practical methodology for the development of new applications. We report the assembly of two types of nanoreactors based upon poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) diblock copolymers as scaffold, uricase and lactoperoxidase as bio-catalysts located within the nanoreactors, and melittin as the biopores inserted into the hydrophobic shell. The nanoreactors were immobilized on poly(2-hydroxyethyl methacrylate)-co-poly(2-aminoethyl methacrylate hydrochloride) (PHEMA-co-P(2-AEMA·HCl) brushes-grafted wafer surfaces by utilizing the strong supramolecular interactions between biotin and streptavidin. The (PHEMA-co-P(2-AEMA·HCl) brushes on silicon surfaces were prepared by a surface initiating atom transfer radical polymerization (ATRP) "graft-from" technique. Cascade reactions between different surface-anchored nanoreactors were demonstrated by converting Amplex® Red to the fluorescent probe resorufin by using the H2O2 produced from uric acid and H2O. The detailed properties of the nanoreactors on the functionalized surface including the binding behaviours and cascade reactions were investigated using emission spectroscopy, transmission electron microscopy (TEM), light scattering (LS), atomic force microscopy (AFM) and a quartz crystal microbalance (QCM-D). The results are proof-of-principle for the preparation of catalytically functional engineered surface materials and lay the foundation for applying this advanced functional surface material in biosensing, implanting and antimicrobial materials preparation.

pH-Responsive Pickering Foams Generated by Surfactant-Free Soft Hydrogel Particles.

Pickering foams are foams stabilized by particles and are generally known to have good stability. A special subclass of particle-stabilized foams includes stimuli-responsive Pickering foams that can be formed or deconstructed by applying an external stimuli or changing the environmental conditions; such intelligent particles could find use in many practical applications. Here, we synthesized surfactant-free biocompatible poly[2(diethylamino)ethyl methacrylate] (PDEAEMA) hydrogel particles (HGPs) by emulsion polymerization. The morphology, structure, and surface charge of the HGPs were characterized by TEM, DLS, and the zeta potential, respectively. We have observed that the pH values of the aqueous solution have a strong influence on the formation of the Pickering foams in the presence of PDEAEMA HGPs. Namely, at pH values ≤4.0 no Pickering foams were produced, while at pH values >4.0 stable Pickering foams were formed. Moreover, the height, size and bubble size distribution of Pickering foams are strongly influenced by the pH values of aqueous solution and PDEAEMA HGPs concentration. The formed Pickering foams in basic aqueous solution can all be conveniently deconstructed by changing the pH values to below 4.0. Interestingly, the dried lamellas of the Pickering foams were constituted by either monolayers or multilayers of PDEAEMA HGPs as demonstrated by SEM.

Contrasting Mechanisms of Spontaneous Adsorption at Liquid-Liquid Interfaces of Nanoparticles Constituted of and Grafted with pH-Responsive Polymers.

Elucidating the mechanisms responsible for spontaneous adsorption of nanoparticles (NPs) at interfaces is important for their application as emulsifiers, bubble stabilizers, or foaming agents. In order to investigate the key factors that control the spontaneous adsorption of NPs at liquid-liquid interfaces, we synthesized seven different types of NPs from pH-responsive polymers poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(2-dimethylamino)ethyl methacrylate) (PDMAEMA) via surfactant-free emulsion polymerization or via "grafting from" polystyrene (PS) NPs. The dynamic interfacial tension (IFT) measurements at the toluene-water (Tol-H2O) interface reveal that when PDEAEMA and PDMAEMA are grafted from the surface of PS NPs the solubility of the grafted pH-responsive polymers in toluene is the key factor determining the NPs' interfacial adsorption. Under acidic conditions (pH < 6.0), PDEAEMA and PDMAEMA are protonated and show no solubility in toluene, and as a result, the grafted NPs do not adsorb at the Tol-H2O interface. Oppositely, under basic conditions (pH > 7.0), PDMAEMA dissolves in toluene and therefore the PDMAEMA-grafted NPs can adsorb at the Tol-H2O interface. Interestingly, when NPs are constituted of PDEAEMA, they can adsorb spontaneously at the Tol-H2O interface under acidic conditions (pH < 6.0) but not under basic conditions (pH > 7.0). In this case, the key factor determining the NPs' spontaneous adsorption at the Tol-H2O interface is the degree of softness of the NPs rather than the solubility of PDEAEMA in toluene. Furthermore, we found that the adsorption of NPs constituted of PDEAEMA- (pH 2.0-6.0) and PDMAEMA-grafted PS NPs (pH 7.0-10.0) at the Tol-H2O interface is a combination of diffusion-controlled and energy-barrier-controlled. The opposite trends observed for the interfacial attachment Δ E and activation energies Ea for the "constituted of" and "grafted from" NPs with pH suggest an opposite mechanisms of adsorption at the Tol-H2O interface. Finally, the synthesized NPs prove to be effective emulsifiers, where the phase of the Pickering emulsions can be changed dynamically by pH adjustment.