A Hybrid Platform Based on a Bispecific Peptide-Antibody Complex for Targeted Cancer Therapy.

Peptide-based therapeutics have suffered from a short plasma half-life. On the other hand, antibodies suffer from poor penetration into solid tumors owing to their large size. Herein, we present a new molecular form, namely a hybrid complex between a hapten-labeled bispecific peptide and an anti-hapten antibody ("HyPEP-body"), that may be able to overcome the aforementioned limitation. The bispecific peptide containing a cotinine tag was synthesized by linking a peptide specific to fibronectin extra domain B (EDB) and a peptide able to bind and inhibit vascular endothelial growth factor (VEGF), yielding cot-biPEPEDB-VEGF . Simple mixing of cot-biPEPEDB-VEGF and anti-cotinine antibody (Abcot ) yielded the hybrid complex, HyPEPEDB-VEGF . HyPEPEDB-VEGF retained the characteristics of the included peptides, and showed improved pharmacokinetic behavior. Moreover, HyPEPEDB-VEGF showed tumor growth inhibition with excellent tumor accumulation and penetration. These findings suggest that the hybrid platform described here offers a solution for most peptide therapeutics that suffer from a short circulation half-life in blood.

Biocompatible Liquid Embolic for the Treatment of Microvascular Hemorrhage.

Persistent or recurrent bleeding from microvessels inaccessible for direct endovascular intervention is a major problem in medicine today. Here, an innovative catheter-directed liquid embolic (P-LE) is bioengineered for rapid microvessel embolization to treat small vessel hemorrhage. Tested in rodent, porcine, and canine animal models under normal and coagulopathic conditions, P-LE outperformed clinically used embolic materials in both survival and non-survival experiments, effectively occluding vessels as small as 40 microns with no signs of recanalization. P-LE occlusion is independent of the coagulation cascade, and its resistance to displacement is ≈ 8 times greater than systolic blood pressure. P-LE is also found to be biocompatible and x-ray visible and does not require polymerization or a chemical reaction to embolize. To simulate the clinical scenario, acute microvascular hemorrhage is created in the pig kidney, liver, or stomach; these are successfully treated with P-LE achieving immediate hemostasis. Furthermore, P-LE is found to be bactericidal to highly resistant patient-derived bacteria, suggesting that P-LE may also protect against infectious complications that may occur following embolization procedures. P-LE is safe, easy to use, and effective in treating -microvessel hemorrhage.

Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization.

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient-derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo- and immunotherapy response in solid tumors.

Noninvasive ROS imaging and drug delivery monitoring in the tumor microenvironment.

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn2+)-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn2+, which induces T1-weighted MRI signal enhancement. Mn@BRNPs show more rapid and greater MRI signal enhancement in high ROS-producing A549 lung carcinoma cells compared with low ROS-producing DU145 prostate cancer cells. A pseudo three-compartment model devised for the ROS-reactive MRI probe enables mapping of the distribution and concentration of ROS within the tumor. Furthermore, doxorubicin-loaded, cancer-targeting ligand biotin-conjugated Dox/Mn@bt-BRNPs show considerable accumulation in A549 tumors and also effectively inhibit tumor growth without causing body weight loss, suggesting their usefulness as a new theranostic agent. Collectively, these findings suggest that Mn@bt-BRNPs could be used as an imaging probe capable of detecting ROS levels and monitoring drug delivery in the TME with potential applicability to other inflammatory diseases.

Longitudinal Magnetic Resonance Imaging with ROS-Responsive Bilirubin Nanoparticles Enables Monitoring of Nonalcoholic Steatohepatitis Progression to Cirrhosis.

Despite the vital importance of monitoring the progression of nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), an efficient imaging modality that is readily available at hospitals is currently lacking. Here, a new magnetic-resonance-imaging (MRI)-based imaging modality is presented that allows for efficient and longitudinal monitoring of NAFLD and NASH progression. The imaging modality uses manganese-ion (Mn2+)-chelated bilirubin nanoparticles (Mn@BRNPs) as a reactive-oxygen-species (ROS)-responsive MRI imaging probe. Longitudinal T1-weighted MR imaging of NASH model mice is performed after injecting Mn@BRNPs intravenously. The MR signal enhancement in the liver relative to muscle gradually increases up to 8 weeks of NASH progression, but decreases significantly as NASH progresses to the cirrhosis-like stage at weeks 10 and 12. A new dual input pseudo-three-compartment model is developed to provide information on NASH stage with a single MRI scan. It is also demonstrated that the ROS-responsive Mn@BRNPs can be used to monitor the efficacy of potential anti-NASH drugs with conventional MRI. The findings suggest that the ROS-responsive Mn@BRNPs have the potential to serve as an efficient MRI contrast for monitoring NASH progression and its transition to the cirrhosis-like stage.

Tissue Ablation: Applications and Perspectives.

Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Photomedicine based on heme-derived compounds.

Photoimaging and phototherapy have become major platforms for the diagnosis and treatment of various health complications. These applications require a photosensitizer (PS) that is capable of absorbing light from a source and converting it into other energy forms for detection and therapy. While synthetic inorganic materials such as quantum dots and gold nanorods have been widely explored for their medical diagnosis and photodynamic (PDT) and photothermal (PTT) therapy capabilities, translation of these technologies has lagged, primarily owing to potential cytotoxicity and immunogenicity issues. Of the various photoreactive molecules, the naturally occurring endogenous compound heme, a constituent of red blood cells, and its derivatives, porphyrin, biliverdin and bilirubin, have shown immense potential as noteworthy candidates for clinically translatable photoreactive agents, as evidenced by previous reports. While porphyrin-based photomedicines have attracted significant attention and are well documented, research on photomedicines based on two other heme-derived compounds, biliverdin and bilirubin, has been relatively lacking. In this review, we summarize the unique photoproperties of heme-derived compounds and outline recent efforts to use them in biomedical imaging and phototherapy applications.

Impeding the Medical Protective Clothing Contamination by a Spray Coating of Trifunctional Polymers.

The risk of fomite-mediated transmission in the clinic is substantially increasing amid the recent COVID-19 pandemic as personal protective equipment (PPE) of hospital workers is easily contaminated by direct contact with infected patients. In this context, it is crucial to devise a means to reduce such transmission. Herein, we report an antimicrobial, antiviral, and antibiofouling trifunctional polymer that can be easily coated onto the surface of medical protective clothing to effectively prevent pathogen contamination on the PPE. The coating layer is formed on the surfaces of PPE by the simple spray coating of an aqueous solution of the trifunctional polymer, poly(dodecyl methacrylate (DMA)-poly(ethylene glycol) methacrylate (PEGMA)-quaternary ammonium (QA)). To establish an optimal ratio of antifouling and antimicrobial functional groups, we performed antifouling, antibacterial, and antiviral tests using four different ratios of the polymers. Antifouling and bactericidal results were assessed using Staphylococcus aureus, a typical pathogenic bacterium that induces an upper respiratory infection. Regardless of the molar ratio, polymer-coated PPE surfaces showed considerable antiadhesion (∼65-75%) and antibacterial (∼75-87%) efficacies soon after being in contact with pathogens and maintained their capability for at least 24 h, which is sufficient for disposable PPEs. Further antiviral tests using coronaviruses showed favorable results with PPE coated at two specific ratios (3.5:6:0.5 and 3.5:5.5:1) of poly(DMA-PEGMA-QA). Moreover, biocompatibility assessments using the two most effective polymer ratios showed no recognizable local or systemic inflammatory responses in mice, suggesting the potential of this polymer for immediate use in the field.

Combination of a STAT3 inhibitor with anti-PD-1 immunotherapy is an effective treatment regimen for a vemurafenib-resistant melanoma.

Patients with BRAFV600E-mutant melanoma are effectively treated with the BRAF-inhibiting drug, vemurafenib, but soon develop drug resistance, limiting vemurafenib's therapeutic efficacy. Constitutive activation of STAT3 in cancer cells and immune cells in the tumor microenvironment (TME) is a crucial contributor to the development of drug resistance and immune evasion in most cancers. Here, we investigated the antitumor efficacy and TME remodeling by APTSTAT3-9R, a cell-permeable STAT3 inhibitory peptide, as a strategy to treat vemurafenib-resistant melanoma. We found that vemurafenib-resistant melanoma remodels into immunosuppressive TME by increasing the expression of specific chemokines to facilitate the infiltration of immunosuppressive immune cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Intratumoral treatment of APTSTAT3-9R led to a reduction in the population of MDSCs and TAMs, while increasing infiltration of cytotoxic T lymphocytes in the TME. Moreover, combination therapy with APTSTAT3-9R and an anti-PD-1 antibody enhanced significant suppression of tumor growth by decreasing infiltration of these immunosuppressive immune cells while increasing the infiltration and cytotoxicity of CD8+ T cells. These findings suggest that combined blockade of STAT3 and PD-1 signaling pathways may be an effective treatment option for overcoming poor therapeutic outcomes associated with drug-resistant BRAF-mutant melanoma.

Systematic Screening and Therapeutic Evaluation of Glyconanoparticles with Differential Cancer Affinities for Targeted Cancer Therapy.

Cancer-targeting ligands used for nanomedicines have been limited mostly to antibodies, peptides, aptamers, and small molecules thus far. Here, a library of glycocalyx-mimicking nanoparticles as a platform to enable screening and identification of cancer-targeting nanomedicines is reported. Specifically, a library of 31 artificial glycopolymers composed of either homogeneous or heterogeneous display of five different sugar moieties (ß-glucose, ß-galactose, α-mannose, ß-N-acetyl glucosamine, and ß-N-acetyl galactosamine) is converted to a library of glyconanoparticles (GlyNPs). GlyNPs optimal for targeting CT26, DU145, A549, and PC3 tumors are systematically screened and identified. The cypate-conjugated GlyNP displaying α-mannose and ß-N-acetyl glucosamine show selective targeting and potent photothermal therapeutic efficacy against A549 human lung tumors. The docetaxel-contained GlyNP displaying ß-glucose, ß-galactose, and α-mannose demonstrate targeted chemotherapy against DU145 human prostate tumors. The results presented herein collectively demonstrate that the GlyNP library is a versatile platform enabling the identification of cancer-targeting glyconanoparticles and suggest its potential applicability for targeting various diseased cells beyond cancer.

Biomimetic lipid Nanocomplexes incorporating STAT3-inhibiting peptides effectively infiltrate the lung barrier and ameliorate pulmonary fibrosis.

Activation of signal transducer and activator of transcription 3 (STAT3) under conditions of inflammation plays a crucial role in the pathogenesis of life-threatening pulmonary fibrosis (PF), initiating pro-fibrotic signaling following its phosphorylation. While there have been attempts to interfere with STAT3 activation and associated signaling as a strategy for ameliorating PF, potent inhibitors with minimal systemic toxicity have yet to be developed. Here, we assessed the in vitro and in vivo therapeutic effectiveness of a cell-permeable peptide inhibitor of STAT3 phosphorylation, designated APTstat3-9R, for ameliorating the indications of pulmonary fibrosis. Our results demonstrate that APTstat3-9R formulated with biomimetic disc-shaped lipid nanoparticles (DLNPs) markedly enhanced the penetration of pulmonary surfactant barrier and alleviated clinical symptoms of PF while causing negligible systemic cytotoxicity. Taken together, our findings suggest that biomimetic lipid nanoparticle-assisted pulmonary delivery of APTstat3-9R may be a feasible therapeutic option for PF in the clinic, and could be applied to treat other fibrotic diseases.

A bilirubin-derived nanomedicine attenuates the pathological cascade of pulmonary fibrosis.

Pulmonary fibrosis is an irreparable and life-threatening disease with only limited therapeutic options. The recent outbreak of COVID-19 has caused a sharp rise in the incidence of pulmonary fibrosis owing to SARS-CoV-2 infection-mediated acute respiratory distress syndrome (ARDS). The considerable oxidative damage caused by locally infiltrated immune cells plays a crucial role in ARDS, suggesting the potential use of antioxidative therapeutics. Here, we report the therapeutic potential of nanoparticles derived from the endogenous antioxidant and anti-inflammatory bile acid, bilirubin (BRNPs), in treating pulmonary fibrosis in a bleomycin-induced mouse model of the disease. Our results demonstrate that BRNPs can effectively reduce clinical signs in mice, as shown by histological, disease index evaluations, and detection of biomarkers. Our findings suggest that BRNPs, with their potent antioxidant and anti-inflammatory effects, long blood circulation half-life, and preferential accumulation at the inflamed site, are potentially a viable clinical option for preventing Covid-19 infection-associated pulmonary fibrosis.

Bilirubin nanomedicine ameliorates the progression of experimental autoimmune encephalomyelitis by modulating dendritic cells.

Although the cause of multiple sclerosis (MS) is unclear, an autoimmune attack on myelin-based coating layers of nerve cells in the brain and spinal cord is the main feature of the disease, highlighting modulation of the immune response to myelin as a feasible therapeutic approach. Here, we report the potential of bilirubin nanoparticles (BRNPs) based on the endogenous antioxidant and anti-inflammatory agent, bilirubin, as a therapeutic nanomedicine for MS. In a mouse model of experimental autoimmune encephalomyelitis (EAE), multiple intravenous injections of BRNPs significantly delayed disease onset and suppressed disease progression and severity as well as disease incidence rate without systemic immunosuppression. Following intravenous injection, BRNPs accumulated more extensively and were retained longer in secondary lymphoid organs of EAE-induced mice compared with non-immunized control mice, including in inguinal lymph nodes (iLNs) and spleens, where antigen presenting cells (APCs) activated by the myelin antigen are abundant. Studies of the underlying mechanism of action further revealed that BRNPs negatively regulated the differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells by inhibiting maturation of APCs through scavenging of reactive oxygen species (ROS) overproduced in both dendritic cells (DCs) and macrophages upon antigen uptake. These findings indicate that BRNPs have the potential to be used as a new therapeutic nanomedicine for treatment of various CD4+ T cell-associated autoimmune diseases.

Nanoparticles Derived from the Natural Antioxidant Rosmarinic Acid Ameliorate Acute Inflammatory Bowel Disease.

Rosmarinic acid (RA), one of the most important polyphenol-based antioxidants, has received growing interest because of its bioactive properties, including anti-inflammatory, anticancer, and antibacterial activities. Despite the high therapeutic potential of RA, its intrinsic properties of poor water solubility and low bioavailability have limited its translation into the clinic. Here, we report on the synthesis and preparation of PEGylated RA-derived nanoparticles (RANPs) and their use as a therapeutic nanomedicine for treatment of inflammatory bowel disease (IBD) in a dextran sulfate sodium (DSS)-induced acute colitis mouse model. PEGylated RA, synthesized via a one-step process from RA and a PEG-containing amine, self-assembled in buffer to form nanoparticles (RANPs) with a diameter of 63.5 ± 4.0 nm. The resulting RANPs showed high colloidal stability in physiological medium up to 2 weeks. RANPs were capable of efficiently scavenging H2O2, thereby protecting cells from H2O2-induced damage. Furthermore, the corticosteroid drug, dexamethasone (DEX), could be loaded into RANPs and released in response to a reactive oxygen species stimulus. Intravenously administered RANPs exhibited significantly improved pharmacokinetic parameters compared with those of the parent RA and were preferentially localized to the inflamed colon. Intravenous administration of RANPs in DSS-induced colitis mice substantially mitigated colonic inflammation in a dose-dependent manner compared with the parent RA, as evidenced by significantly reduced disease activity index scores, body weight loss, and colonic inflammatory damage. In addition, RANPs suppressed expression and production of typical pro-inflammatory cytokines in the inflamed colon. Furthermore, DEX-loaded RANPs showed enhanced therapeutic efficacy in the colitis model compared with bare RANPs at the equivalent dose, indicating synergy with a conventional medication. These findings suggest that RANPs deserve further consideration as a potential therapeutic nanomedicine for the treatment of various inflammatory diseases, including IBD.

Gold nanorods with an ultrathin anti-biofouling siloxane layer for combinatorial anticancer therapy.

Despite the wide utility of gold nanorods (GNRs) in biomedical fields, only a few methods for modifying or coating the surface of GNRs suitable for biomedical applications are available. In this study, we report a new facile method that enables formation of an ultra-thin (nanometre-thickness) siloxane layer on GNRs with anti-biofouling properties and ligand functionalisation ability. A triblock random copolymer, poly(TMSMA-r-PEGMA-r-NAS), was used to coat GNRs. An ultrathin polymeric shell was formed surrounding GNRs through acid-catalysed crosslinking of silicates of TMSMA. The polymer-coated GNRs (p-GNRs) exhibited high colloidal stability in biological solutions of high ionic strength and long-term stability superior to that of PEG2k-S-GNRs. The functionalities of NAS were demonstrated using two methods for conjugating targeting ligands and loading doxorubicin via electrostatic interactions. The ligand-specific cancer-targeting ability and combinatorial chemo-photothermal anticancer effects were validated in vitro and in vivo, suggesting their potential utility in various fields.

Bilirubin nanomedicine alleviates psoriatic skin inflammation by reducing oxidative stress and suppressing pathogenic signaling.

Psoriasis is a prevalent chronic inflammatory skin disease characterized by thickening of the epidermis accompanied by lesional erythema, scaling, and induration as a result of abnormal proliferation of keratinocytes. During the development of psoriasis, levels of intracellular reactive oxygen species (ROS) within psoriatic lesions are elevated, activating a pro-inflammatory signaling cascade. Here, we evaluated the therapeutic efficacy and mode of action of bilirubin nanoparticles (BRNPs), based on the potent, endogenous antioxidant bilirubin, in a preclinical psoriasis model. We found that topical treatment of psoriatic lesions with BRNPs effectively attenuated upregulation of intracellular ROS levels within keratinocytes and ameliorated the symptoms of psoriasis. A subsequent mechanistic study showed that preventing oxidative stress in activated keratinocytes suppressed the secretion of inflammatory mediators and recruitment of immune cells. Subsequent expression of the antigen-presenting cell (APC) maturation markers, class II major histocompatibility complex (MHC class II), cluster of differentiation (CD) 80 and CD86, was significantly decreased, resulting in a reduction in the differentiation of naïve CD4+ T cells into interleukin (IL)-17-producing T-helper (Th) 17 cells. Unlike the commercial corticosteroid drug, clobetasol propionate (CLQ), BRNPs, composed of the endogenous antioxidant bilirubin and the approved polymer polyethylene glycol (PEG), did not exert systemic cytotoxicity. Collectively, these findings highlight the potential of BRNPs as a novel nanomedicine for ameliorating psoriasis-like skin inflammation through topical treatment and suggest that their use could be further expanded to treat other chronic skin inflammation diseases, including atopic dermatitis.

Tubulin-Based Nanotubes as Delivery Platform for Microtubule-Targeting Agents.

Tubulin-based nanotubes (TNTs) to deliver microtubule-targeting agents (MTAs) for clinical oncology are reported. Three MTAs, docetaxel (DTX), laulimalide (LMD), and monomethyl auristatin E (MMAE), which attach to different binding sites in a tubulin, are loaded onto TNTs and cause structural changes in them, including shape anisotropy and tubulin layering. This drug-driven carrier transformation leads to changes in the drug-loading efficiency and stability characteristics of the carrier. TNTs coloaded with DTX and LMD efficiently deliver dual drug cargoes to cellular tubulins by the endolysosomal pathway, and results in synergistic anticancer and antiangiogenic action of the drugs in vitro. In in vivo tests, TNTs loaded with a microtubule-destabilizing agent MMAE suppress the growth of tumors with much higher efficacy than free MMAE did. This work suggests a new concept of using a drug's target protein as a carrier. The findings demonstrate that the TNTs developed here can be used universally as a delivery platform for many MTAs.

Prevention of Bacterial Colonization on Catheters by a One-Step Coating Process Involving an Antibiofouling Polymer in Water.

As reports of multidrug resistant pathogens have increased, patients with implanted medical catheters increasingly need alternative solutions to antibiotic treatments. As most catheter-related infections are directly associated with biofilm formation on the catheter surface, which, once formed, is difficult to eliminate, a promising approach to biofilm prevention involves inhibiting the initial adhesion of bacteria to the surface. In this study, we report an amphiphilic, antifouling polymer, poly(DMA-mPEGMA-AA) that can facilely coat the surfaces of commercially available catheter materials in water and prevent bacterial adhesion to and subsequent colonization of the surface, giving rise to an antibiofilm surface. The antifouling coating layer was formed simply by dipping a model substrate (polystyrene, PET, PDMS, or silicon-based urinary catheter) in water containing poly(DMA-mPEGMA-AA), followed by characterization by X-ray photoelectron spectroscopy (XPS). The antibacterial adhesion properties of the polymer-coated surface were assessed for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) growth under static (incubation in the presence of a bacterial suspension) and dynamic (bacteria suspended in a solution under flow) conditions. Regardless of the conditions, the polymer-coated surface displayed significantly reduced attachment of the bacteria (antiadhesion effect > ∼8-fold) compared to the bare noncoated substrates. Treatment of the implanted catheters with S. aureus in vivo further confirmed that the polymer-coated silicon urinary catheters could significantly reduce bacterial adhesion and biofilm formation in a bacterial infection animal model. Furthermore, the polymer-coated catheters did not induce hemolysis and were resistant to the adhesion of blood-circulating cells, indicative of high biocompatibility. Collectively, the present amphiphilic antifouling polymer is potentially useful as a coating platform that renders existing medical devices resistant to biofilm formation.