Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing.

The extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell-material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge. Here, near-infrared (NIR)-controlled multifunctional hydrogel platforms, named PIC/CM@NPs, are introduced to dictate fibroblast behavior during wound healing by tuning the matrix oxidative stress and mechanical tensions. PIC/CM@NPs are prepared through cell adhesion-medicated assembly of collagen-like polyisocyanide (PIC) polymers and cell-membrane-coated conjugated polymer nanoparticles (CM@NPs), which closely mimic the fibrous structure and nonlinear mechanics of ECM. Upon NIR stimulation, PIC/CM@NPs composites enhance fibroblast cell proliferation, migration, cytokine production, and myofibroblast activation, crucial for wound closure. Moreover, they exhibit effective and toxin removal antibacterial properties, reducing inflammation. This multifunctional approach accelerates healing by 95%, highlighting the importance of integrating biochemical and biophysical cues in the biomaterial design for advanced tissue regeneration.

Antioxidant and Immunomodulatory Polymer Vesicles for Effective Diabetic Wound Treatment through ROS Scavenging and Immune Modulating.

Chronic diabetic wound patients usually show high glucose levels and systemic immune disorder, resulting in high reactive oxygen species (ROS) levels and immune cell dysfunction, prolonged inflammation, and delayed wound healing. Herein, we prepared an antioxidant and immunomodulatory polymer vesicle for diabetic wound treatment. This vesicle is self-assembled from poly(ε-caprolactone)36-block-poly[lysine4-stat-(lysine-mannose)22-stat-tyrosine)16] ([PCL36-b-P[Lys4-stat-(Lys-Man)22-stat-Tyr16]). Polytyrosine is an antioxidant polypeptide that can scavenge ROS. d-Mannose was introduced to afford immunomodulatory functions by promoting macrophage transformation and Treg cell activation through inhibitory cytokines. The mice treated with polymer vesicles showed 23.7% higher Treg cell levels and a 91.3% higher M2/M1 ratio than those treated with PBS. Animal tests confirmed this vesicle accelerated healing and achieved complete healing of S. aureus-infected diabetic wounds within 8 days. Overall, this is the first antioxidant and immunomodulatory vesicle for diabetic wound healing by scavenging ROS and regulating immune homeostasis, opening new avenues for effective diabetic wound healing.

Mechanism of Action and Design of Potent Antibacterial Block Copolymer Nanoparticles.

Self-assembled polymer nanoparticles are promising antibacterials, with nonspherical morphologies of particular interest as recent work has demonstrated enhanced antibacterial activity relative to their spherical counterparts. However, the reasons for this enhancement are currently unclear. We have performed a multifaceted analysis of the antibacterial mechanism of action of 1D nanofibers relative to nanospheres by the use of flow cytometry, high-resolution microscopy, and evaluations of the antibacterial activity of pristine and tetracycline-loaded nanoparticles. Low-length dispersity, fluorescent diblock copolymer nanofibers with a crystalline poly(fluorenetrimethylenecarbonate) (PFTMC) core (length = 104 and 472 nm, height = 7 nm, width = 10-13 nm) and a partially protonated poly(dimethylaminoethyl methacrylate) (PDMAEMA) corona (length = 12 nm) were prepared via seeded growth living crystallization-driven self-assembly. Their behavior was compared to that of analogous nanospheres containing an amorphous PFTMC core (diameter of 12 nm). While all nanoparticles were uptaken into Escherichia coli W3110, crystalline-core nanofibers were observed to cause significant bacterial damage. Drug loading studies indicated that while all nanoparticle antibacterial activity was enhanced in combination with tetracycline, the enhancement was especially prominent when small nanoparticles (ca. 15-25 nm) were employed. Therefore, the identified differences in the mechanism of action and the demonstrated consequences for nanoparticle size and morphology control may be exploited for the future design of potent antibacterial agents for overcoming antibacterial resistance. This study also reinforces the requirement of morphological control over polymer nanoparticles for biomedical applications, as differences in activity are observed depending on their size, shape, and core-crystallinity.

Collapsed Star Copolymers Exhibiting Near Perfect Mimicry of the Therapeutic Protein "TRAIL".

Here we introduce amphiphilic star polymers as versatile protein mimics capable of approximating the activity of certain native proteins. Our study focuses on designing a synthetic polymer capable of replicating the biological activity of TRAIL, a promising anticancer protein that shows very poor circulation half-life. Successful protein mimicry requires precise control over the presentation of receptor-binding peptides from the periphery of the polymer scaffold while maintaining enough flexibility for protein-peptide binding. We show that this can be achieved by building hydrophobic blocks into the core of a star-shaped polymer, which drives unimolecular collapse in water. By screening a library of diblock copolymer stars, we were able to design structures with IC50's of ∼4 nM against a colon cancer cell line (COLO205), closely approximating the activity of the native TRAIL protein. This finding highlights the broad potential for simple synthetic polymers to mimic the biological activity of complex proteins.

Hypoxia Reversion by Low-Immunogenic Ultra-Acid-Sensitive Comicelles of Protein-Polymer Conjugates Sensitizes Tumors to Photodynamic Therapy.

Hypoxia is characteristic of the tumor microenvironment, which is correlated with resistance to photodynamic therapy (PDT), radiotherapy, chemotherapy, and immunotherapy. Catalase is potentially useful to catalyze the conversion of endogenous H2O2 to O2 for hypoxia reversion. However, the efficient delivery of catalase into the hypoxia regions of tumors is a huge challenge. Here, we report the self-assembly of ultra-acid-sensitive polymer conjugates of catalase and albumin into nanomicelles that are responsive to the acidic tumor microenvironment. The immunogenicity of catalase is mitigated by the presence of albumin, which reduces the cross-linking of catalase with B cell receptors, resulting in improved pharmacokinetics. The ultra acid sensitivity of the nanomicelles makes it possible to efficiently escape the lysosomal degradation after endocytosis and permeate into the interior of tumors to reverse hypoxia in vitro and in vivo. In mice bearing triple-negative breast cancer, the nanomicelles loaded with a photosensitizer effectively accumulate and penetrate into the whole tumors to generate a sufficient amount of O2 to reverse hypoxia, leading to enhanced efficacy of PDT without detectable side effects. These findings provide a general strategy of self-assembly to design low-immunogenic ultra-acid-sensitive comicelles of protein-polymer conjugates to reverse tumor hypoxia, which sensitizes tumors to PDT.

Proteomimetic Polymers Trigger Potent Antigen-Specific T Cell Responses to Limit Tumor Growth.

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8+ T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.

Coacervate Dense Phase Displaces Surface-Established Pseudomonas aeruginosa Biofilms.

For millions of years, barnacles and mussels have successfully adhered to wet rocks near tide-swept seashores. While the chemistry and mechanics of their underwater adhesives are being thoroughly investigated, an overlooked aspect of marine organismal adhesion is their ability to remove underlying biofilms from rocks and prepare clean surfaces before the deposition of adhesive anchors. Herein, we demonstrate that nonionic, coacervating synthetic polymers that mimic the physicochemical features of marine underwater adhesives remove ∼99% of Pseudomonas aeruginosa (P. aeruginosa) biofilm biomass from underwater surfaces. The efficiency of biofilm removal appears to align with the compositional differences between various bacterial biofilms. In addition, the surface energy influences the ability of the polymer to displace the biofilm, with biofilm removal efficiency decreasing for surfaces with lower surface energies. These synthetic polymers weaken the biofilm-surface interactions and exert shear stress to fracture the biofilms grown on surfaces with diverse surface energies. Since bacterial biofilms are 1000-fold more tolerant to common antimicrobial agents and pose immense health and economic risks, we anticipate that our unconventional approach inspired by marine underwater adhesion will open a new paradigm in creating antibiofilm agents that target the interfacial and viscoelastic properties of established bacterial biofilms.

A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy.

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy. This structure promoted H-aggregation and intersystem crossing of NBS, resulting in a ∼ 3-fold amplification in superoxide anion and singlet oxygen generation. The photodynamic therapy directly damaged hypoxia tumor cells and stimulated the proliferation of NK cells and cytotoxic T lymphocytes, thereby sensitizing STING immunotherapy. A single systemic intravenous administration of PNBS/diABZI eradicated orthotopic mammary tumors in murine models, achieving long-term antitumor immune memory to inhibit tumor recurrence and metastasis and significantly improving long-term tumor-free survival. This work provides a design rule for boosting reactive oxygen species production by promoting the intersystem crossing process, highlighting the potential of Type I photosensitizer-polymer vehicles for augmenting STING immunotherapy.

Antibacterial Hydrogel Adhesives Based on Bifunctional Telechelic Dendritic-Linear-Dendritic Block Copolymers.

Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.

Rejuvenating silicon probes for acute neurophysiology.

Neurophysiological recording with a new probe often yields better signal quality than with a used probe. Why does the signal quality degrade after only a few experiments? Here, we considered silicon probes in which the contacts are densely packed, and each contact is coated with a conductive polymer that increases its surface area. We tested 12 Cambridge Neurotech silicon probes during 61 recording sessions from the brain of three marmosets. Out of the box, each probe arrived with an electrodeposited polymer coating on 64 gold contacts and an impedance of around 50 kΩ. With repeated use, the impedance increased and there was a corresponding decrease in the number of well-isolated neurons. Imaging of the probes suggested that the reduction in signal quality was due to a gradual loss of the polymer coating. To rejuvenate the probes, we first stripped the contacts, completely removing their polymer coating, and then recoated them in a solution of 10 mM 3,4-Ethylenedioxythiophene (EDOT) monomer with 11 mM Poly(sodium 4-styrenesulfonate) (PSS) using a current density of about 3 mA/cm2 for 30 s. This recoating process not only returned probe impedance to around 50 kΩ but also yielded significantly improved signal quality during neurophysiological recordings. Thus, insertion into the brain promoted the loss of the polymer that coated the contacts of the silicon probes. This led to degradation of signal quality, but recoating rejuvenated the probes.NEW & NOTEWORTHY With repeated use, a silicon probe's ability to isolate neurons degrades. As a result, the probe is often discarded after only a handful of uses. Here, we demonstrate a major source of this problem and then produce a solution to rejuvenate the probes.

Future Nanotechnology-Based Strategies for Improved Management of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.

Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self- and Metal-Induced α-Synuclein Aggregation.

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α-synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self-induced aggregation of α-synuclein into amyloid-type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII-induced α-synuclein aggregation.

Antimicrobial Peptide Assembly on Zwitterionic Polymer Films to Slow Down Biofilm Formation.

Formation of biofilms on equipment used in various fields, such as medicine, domestic sanitation, and marine transportation, can cause serious problems. The use of antibiofouling and bactericidal modifications is a promising strategy for inhibiting bacterial adhesion and biofilm formation. To further enhance the antibiofilm properties of a surface, various combinations of bactericidal modifications alongside antibiofouling modifications have been developed. Optimization of the arrangements of antimicrobial peptides on the antibiofouling surface would allow us to design longer-life antibiofilm surface modifications. In this study, a postmodification was conducted with different design using the antimicrobial peptide KR12 on an antibiofouling copolymer film consisting of 2-methacryloyloxyethyl phosphorylcholine, 3-methacryloxypropyl trimethoxysilane, and 3-(methacryloyloxy) propyl-tris(trimethylsilyloxy) silane. The distance of KR12 from the film was adjusted by combining different lengths of poly(ethylene glycol) (PEG) spacers (molecular weights are 2000 and 5000). The density of KR12 was ranged from 0.06 to 0.22 nm-2. When these modified surfaces were exposed to a nutrient-rich TSB suspension, the bacterial area formed by E. coli covered 5-127% of the original copolymer film. We found that a significant distance between the bactericidal and antibiofouling modifications, along with a higher density of bactericidal modifications, slows down the biofilm formation.

Development of Transdermal Formulation Integrating Polymer-Based Solid Microneedles and Thermoresponsive Gel Fucoidan for Antiaging: Proof of Concept Study.

Skin can be damaged by intense and prolonged exposure to ultraviolet (UV) radiation. Photoaging and acute damage from sun exposure result in collagen degradation and enzymatic activity decline in the skin. Fucoidan (FUC) exhibits potential antiaging properties, including collagen synthesis promotion and enzyme activity inhibition. However, FUC's limited ability to penetrate the skin layers due to its large molecular weight makes it a challenge for topical application. In this study, we successfully developed a new approach by integrating thermoresponsive gel (TRG) containing FUC with solid microneedles (SMNs) as a delivery system. TRG is formulated using a combination of Pluronic F127 (PF127) and Pluronic F68 (PF68) polymers, while SMNs are made from a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers with a variety of cross-linkers. Based on the results of ex vivo testing, it was shown that more than 80% of FUC can be delivered using the optimized formula. Furthermore, the results of the in vitro blood hemolytic test showed that TRG-FUC-SMNs were relatively biocompatible. In vivo antiaging activity tests using a rat model exposed to UV for 14 days showed that histological assessment, skin elasticity measurement, wrinkle evaluation, and skin moisture content had no significant differences (p < 0.05) compared to the positive control group. In contrast, a significant difference (p < 0.05) was observed when comparing the TRG-FUC-SMNs group with the group that received only TRG-FUC without pretreatment and negative controls. These findings suggest that FUC has potential to be delivered using the TRG system in combination with SMNs to harness its antiaging properties.

Mussel-Inspired Polymer-Based Coating Technology for Antifouling and Antibacterial Properties.

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.

Photostimulated Extended Nitric Oxide (NO) Release from Water-Soluble Block Copolymer to Enhance Antibacterial Activity.

N-Nitrosamines are well established motifs to release nitric oxide (NO) under photoirradiation. Herein, a series of amphiphilic N-nitrosamine-based block copolymers (BCPx-NO) are developed to attain controlled NO release under photoirradiation (365 nm, 3.71 mW/cm2). The water-soluble BCPx-NO forms micellar architecture in aqueous medium and exhibits a sustained NO release of 92-160 µM within 11.5 h, which is 36.8-64.0% of the calculated value. To understand the NO release mechanism, a small molecular NO donor (NOD) resembling the NO releasing functional motif of BCPx-NO is synthesized, which displays a burst NO release in DMSO within 2.5 h. The radical nature of the released NO is confirmed by electron paramagnetic resonance (EPR) spectroscopy. The gradual NO release from micellar BCPx-NO enhances antibacterial activity over NOD and exhibits a superior bactericidal effect on Gram-positive Staphylococcus aureus. In relation to biomedical applications, this work offers a comprehensive insight into tuning light-triggered NO release to improve antibacterial activity.

Low Molecular Weight Shuttle Molecules Enhance Polychloramide Antimicrobial Activity.

Investigated were the influences of succinimide (SI), 5,5-dimethylhydantoin (DMH), and 3-(hydroxymethyl)-5,5-dimethylhydantoin (HDMH) on the biocidal activity of chlorinated, water-soluble polyamide prepared by the reaction of isopropylamine with poly(styrene-alt-maleic anhydride). The resulting polymer was a negatively charged, water-soluble polymer bearing a carboxylic acid and an isopropylamide moiety on nearly every repeat unit. Subsequent treatment with NaOCl chlorinated the polymers to up to 4.4% Cl while inflicting some polymer chain scission. SI, DMH, or HDMH increased the biocidal activity of polychloramides toward planktonic Escherichia coli and Staphylococcus aureus. Independent solution studies confirmed that oxidative chlorine spontaneously transferred from aqueous polychloramides to small molecules. We concluded that SI, DMH, and HDMH acted as shuttles that extracted oxidative Cl from the polymer chloramides and transported oxidative Cl more efficiently to microbial surfaces. Succinimide was the most effective shuttle. These results warn that some low molecular weight soluble molecules in antimicrobial testing solutions may exaggerate the effectiveness of the polymer or immobilized antimicrobial agents.

FAP Targeting of Photosensitizer-Loaded Polymersomes for Increased Light-Activated Cell Killing.

As current chemo- and photodynamic cancer therapies are associated with severe side effects due to a lack of specificity and to systemic toxicity, innovative solutions in terms of targeting and controlled functionality are in high demand. Here, we present the development of a polymersome nanocarrier equipped with targeting molecules and loaded with photosensitizers for efficient uptake and light-activated cell killing. Polymersomes were self-assembled in the presence of photosensitizers from a mixture of nonfunctionalized and functionalized PDMS-b-PMOXA diblock copolymers, the latter designed for coupling with targeting ligands. By encapsulation inside the polymersomes, the photosensitizer Rose Bengal was protected, and its uptake into cells was mediated by the nanocarrier. Inhibitor of fibroblast activation protein α (FAPi), a ligand for FAP, was attached to the polymersomes' surface and improved their uptake in MCF-7 breast cancer cells expressing relatively high levels of FAP on their surface. Once internalized by MCF-7, irradiation of Rose Bengal-loaded FAPi-polymersomes generated reactive oxygen species at levels high enough to induce cell death. By combining photosensitizer encapsulation and specific targeting, polymersomes represent ideal candidates as therapeutic nanocarriers in cancer treatment.