Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

Phytic Acid-Promoted Exfoliation of Black Phosphorus Nanosheets for the Fabrication of Photothermal Antibacterial Coatings.

Medical device-associated infections (MDAI) caused by planktonic pathogens are of serious concern worldwide due to the emergence of drug resistance resulting from continuous overuse or misuse of antibiotics. Therefore, the design of non-antibiotics-based treatment for MDAI is of crucial importance. Black phosphorus (BP), a novel 2D material, has recently received much attention owing to its remarkable physical, chemical, mechanical, and functional features. However, the intricacy of the fabrication process has severely hampered the development of BP in prospective applications. In this study, a simple and eco-friendly liquid-phase exfoliation method of phytic acid (PA)-promoted exfoliation of BP nanosheets (PA@BP NSs) is developed for their potential application in antibacterial photothermal therapy. To impart the antimicrobial effects, the polydimethylsiloxane surfaces are functionalized with quaternized polymer (polyquaternium-2 or PQ) and PA@BP NSs, leading to the formation of PA-BP-PQ composite coatings. In addition to the contact-killing antibacterial effect of the cationic PQ, the PA-BP-PQ coating exhibits remarkable near-infrared irradiation-triggered bactericidal effects with low cytotoxicity both in vitro and in vivo. This study proposes a simple liquid-phase exfoliation technique for the fabrication of BP NSs and a one-step approach for the construction of PA-BP-PQ composite coatings for bi-modal (contact-killing and photothermal) antimicrobial therapy.

Nanoengineering Natural Leather for Dynamic Thermal Management and Electromagnetic Interference Shielding.

Unpredictable and extreme weather conditions, along with increasing electromagnetic pollution, have resulted in a significant threat to human health and productivity, causing irreversible damage to society's well-being and economy. However, existing personal temperature management and electromagnetic protection materials lack adaptability to dynamic environmental changes. To address this, a unique asymmetric bilayer leather/a-MWCNTs/CA fabric is developed by vacuum-infiltrating interconnected a-MWCNTs networks into natural leather's microfiber backbone and spraying porous acetic acid (CA) on the reverse side. Such fabric achieves simultaneous passive radiation cooling, heating, and anti-electromagnetic interference functions without external energy input. The fabric's cooling layer has high solar reflectance (92.0%) and high infrared emissivity (90.2%), providing an average subambient radiation cooling effect of 10 °C, while the heating layer has high solar absorption (98.0%), enabling excellent passive radiative heating and effective compensation for warming via Joule heating. Additionally, the fabric's 3D conductive a-MWCNTs network provides electromagnetic interference shielding effectiveness of 35.0 dB mainly through electromagnetic wave absorption. This multimode electromagnetic shielding fabric can switch between cooling and heating modes to adapt to dynamic cooling and heating scenarios, providing a new avenue for sustainable temperature management and electromagnetic protection applications.

Correction: Polymers as advanced antibacterial and antibiofilm agents for direct and combination therapies.

[This corrects the article DOI: 10.1039/D1SC05835E.].

Bimodal Antimicrobial Surfaces of Phytic Acid-Prussian Blue Nanoparticles-Cationic Polymer Networks.

Surface modification plays a pivotal role in tailoring the functionalities of a solid material. Introduction of antimicrobial function on material surfaces can provide additional protection against life-threatening bacterial infections. Herein, a simple and universal surface modification method based on surface adhesion and electrostatic interaction of phytic acid (PA) is developed. PA is first functionalized with Prussian blue nanoparticles (PB NPs) via metal chelation and then conjugates with cationic polymers (CPs) through electrostatic interaction. With the aid of surface adherent PA and gravitation effect, the as-formed PA-PB-CP network aggregates are deposited on the solid materials in a substrate-independent manner. Synergistic bactericidal effects of "contact-killing" induced by the CPs and localized photothermal effect caused by the PB NPs endow the substrates with strong antibacterial performance. Membrane integrity, enzymatic activity, and metabolism function of the bacteria are disturbed in contact with the PA-PB-CP coating under near-infrared (NIR) irradiation. The PA-PB-CP modified biomedical implant surfaces exhibit good biocompatibility and synergistic antibacterial effect under NIR irradiation, and eliminate the adhered bacteria both in vitro and in vivo.

A Zero-Energy, Zero-Emission Air Conditioning Fabric.

High indoor humidity/temperature pose serious public health threat and hinder industrial productivity, thus adversely impairing the wellness and economy of the entire society. Traditional air conditioning systems for dehumidification and cooling involve significant energy consumption and have accelerated the greenhouse effect. Here, this work demonstrates an asymmetric bilayer cellulose-based fabric that enables solar-driven continuous indoor dehumidification, transpiration-driven power generation, and passive radiative cooling using the same textile without any energy input. The multimode fabric (ABMTF) consists of a cellulose moisture absorption-evaporation layer (ADF) and a cellulose acetate (CA) radiation layer. The ABMTF exhibits a high moisture absorption capacity and water evaporation rate, which quickly reduces the indoor relative humidity (RH) to a comfortable level (40-60% RH) under 1 sun illumination. The evaporation-driven continuous capillary flow generates a maximum open-circuit voltage (Voc ) of 0.82 V, and a power density (P) up to 1.13 µW cm-3 . When a CA layer with high solar reflection and mid-infrared (mid-IR) emissivity faces outward, it realizes subambient cooling of ≈12 °C with average cooling power of ≈106 W m-2 at midday under radiation of 900 W m-2 . This work brings a new perspective to develop the next-generation, high performance environmentally friendly materials for sustainable moisture/thermal management and self-powered applications.

Simultaneous deposition of tannic acid derivative and covalent conjugation of poly(2-methyl-2-oxazoline) for the construction of antifouling coatings.

Bacterial adhesion and subsequent colonization play an important role in the failure of biomedical implants and devices. Thus, development of a simple surface modification strategy to combat bacterial adhesion is highly desirable. In this work, "one-pot" fabrication of antifouling coatings based on simultaneous surface adhesion of trihydroxyphenyl and dihydroxyphenyl moieties of tannic acid (TA) derivative and covalent conjugation of hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) was demonstrated. Surface co-depositions of TA/PMOXA hybrids of different TA derivative to PMOXA weight ratios and different molecular weights of PMOXA were conducted. The surface hydrophilicity and deposition universality on various substrates were investigated. The anti-bacterial and anti-platelet adhesion, as well as anti-biofilm formation abilities, of the TA/PMOXA-based coating were also studied. In vitro hemolysis and cytotoxicity, and in vivo biocompatibility of the TA/PMOXA-based coating were further evaluated. All the results indicate that the TA/PMOXA-based coating could be employed as an antifouling additive on biomedical implants and devices.

Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens.

Nowadays, infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide. Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance (MDR) and limitations with existing therapeutic options. Antibacterial photodynamic therapy (APDT) is a potential therapeutic modality that involves the systematic administration of photosensitizers (PSs), light, and molecular oxygen (O2) for coping with bacterial infections. Although the existing porphyrin and non-porphyrin PSs were effective in APDT, the poor solubility, limited efficacy against Gram-negative bacteria, and non-specific distribution hinder their clinical applications. Accordingly, to promote the efficiency of conventional PSs, various polymer-driven modification and functionalization strategies have been adopted to engineer multifunctional hybrid phototherapeutics. This review assesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications. Further, the key research findings of the following aspects are considered in-depth with constructive discussions: i) PSs-integrated/functionalized polymeric composites through various molecular interactions; ii) PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated infections; and iii) PSs-embedded films, scaffolds, and hydrogels for regenerative medicine applications.

Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy.

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC50 of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.

Cationic porphyrin-based nanoparticles for photodynamic inactivation and identification of bacteria strains.

The emergence of antibiotic drug resistance has undermined the efficacy of antibiotics, and is becoming a severe threat to public health. To combat antibiotic drug resistance and to replace traditional antibiotic treatment, an alternative strategy based on antibacterial photodynamic therapy (APDT), which has broad applicability, high efficiency and less potential of developing antibiotic drug resistance, has been developed. In this work, the cationic porphyrin-based nanoparticles (NPs) were prepared by epoxy-amine chain extension polymerization of diepoxy-terminated poly(ethylene glycol) (PEG) and tetraamino-containing porphyrin, followed by quaternization with methyl iodine and butyl bromide. The as-obtained cationic porphyrin NPs preserved the photophysical properties of porphyrin derivatives, and can efficiently generate singlet oxygen (1O2) under 635 nm laser irradiation. The cationic porphyrin-based NPs displayed intrinsic antibacterial properties, and exhibited strong APDT effect on Gram-positive bacteria by destroying the bacterial cell membranes. Upon incubation with different bacterial strains, it was found that they could be utilized to identify Gram-positive bacteria by observing the sedimentation behavior of their mixtures, and visualizing their co-cultured and centrifugal bacteria cakes. In addition, the cationic porphyrin-based NPs had good hemocompatibility and low dark cytotoxicity.

Polymers as advanced antibacterial and antibiofilm agents for direct and combination therapies.

The growing prevalence of antimicrobial drug resistance in pathogenic bacteria is a critical threat to global health. Conventional antibiotics still play a crucial role in treating bacterial infections, but the emergence and spread of antibiotic-resistant micro-organisms are rapidly eroding their usefulness. Cationic polymers, which target bacterial membranes, are thought to be the last frontier in antibacterial development. This class of molecules possesses several advantages including a low propensity for emergence of resistance and rapid bactericidal effect. This review surveys the structure-activity of advanced antimicrobial cationic polymers, including poly(α-amino acids), ß-peptides, polycarbonates, star polymers and main-chain cationic polymers, with low toxicity and high selectivity to potentially become useful for real applications. Their uses as potentiating adjuvants to overcome bacterial membrane-related resistance mechanisms and as antibiofilm agents are also covered. The review is intended to provide valuable information for design and development of cationic polymers as antimicrobial and antibiofilm agents for translational applications.

Surface co-deposition of polypyrrole nanoparticles and tannic acid for photothermal bacterial eradication.

Bacterial infections on implantable materials can cause severe complications for affected patients, posing a serious threat to human health. Therefore, the development of appropriate surface modification strategies to construct the antibacterial platforms on medical implants are urgently needed. In this work, the poly(vinyl alcohol) (PVA)-stabilized polypyrrole nanoparticles (PVA-PPy NPs) were prepared by oxidative polymerization using FeCl3 as the oxidant. Subsequent mixing of the PVA-PPy NPs solution mixture with tannic acid (TA) was facilitated by hydrogen bonding. The as-formed TA/PVA-PPy NPs can be deposited with good adhesion onto solid materials in a substrate-independent manner. The hydrophilic TA/PVA-PPy NPs-deposited titanium (Ti-TPP) surface can reduce the adhesion of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, the Ti-TPP surface had photothermal property under 808 nm near-infrared (NIR) irradiation, which can kill the adhered bacteria via the hyperthermal effect. Upon exposure to NIR, the respective survival rates of S. aureus and E. coli on the Ti-TPP surfaces were only 1.66% and 2.78%, in comparison to those on the pristine Ti surfaces. Furthermore, the Ti-TPP surface could prevent the formation of early-stage biofilm under NIR irradiation. The TA/PVA-PPy NPs composites can be utilized as a contact-photoactive antibacterial coating for biomedical applications.

Recent progress in tannic acid-driven antibacterial/antifouling surface coating strategies.

Medical devices and surgical implants are necessary for tissue engineering and regenerative medicines. However, the biofouling and microbial colonization on the implant surface continues to be a major concern, which is difficult to eradicate and typically necessitates either antibiotic therapy or implant removal. As a result, efficient and eco-friendly bioinspired coating strategies for tethering functional materials or molecules on different medical substrates are highly desirable, especially for endowing versatile surface functionalities. Tannic acid (TA), a well-known tea stain polyphenol, has a good affinity for various substrates and actively inhibits the adhesion and colonization of microbes. Thus, functionalization of polymers, nanomaterials, metal-phenolic networks (MPNs), and proteins using TA bestows the end-products with unique binding or anchoring abilities on various implantable surfaces. This review addresses the recent advancements in the essential biomedical perspective of TA-based bioinspired universal surface coating technologies by focusing on their intrinsic features and ability to produce engineered functional composites. Further, the possible contributions of TA-based composites in antifouling and antibacterial applications on various biomedical substrates are outlined.

pH-Sensitive Dextran-Based Micelles from Copper-Free Click Reaction for Antitumor Drug Delivery.

There remains a need to develop new strategies to fabricate dextran-based biocompatible drug delivery systems for safe and effective chemotherapy. Herein, a copper-free azide-propiolate ester click reaction was introduced for dextran modification to fabricate a pH-sensitive dextran-based drug delivery system. A pH-sensitive dextran-based micelle system, self-assembled from amphiphilic dextran-graft-poly(2-(diisopropylamino)ethyl methacrylate-co-2-(2',3',5'-triiodobenzoyl)ethyl methacrylate) or dextran-g-P(DPA-co-TIBMA), is reported for effective chemotherapy. The amphiphilic dextran-g-P(DPA-co-TIBMA) was prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization and copper-free azide-propiolate ester click reaction. Doxorubicin (DOX)-loaded dextran-g-P(DPA-co-TIBMA) micelles were prepared through self-assembly of DOX and dextran-g-P(DPA-co-TIBMA) in aqueous solution, and had a mean diameter of 154 nm and a drug loading content of 9.7 wt %. The release of DOX from DOX-loaded dextran-g-P(PDPA-co-TIBMA) micelles was slow at pH 7.4, but was greatly accelerated under acidic conditions (pH 6 and 5). Confocal laser scanning microscopy and flow cytometry experiments showed that the dextran-g-P(DPA-co-TIBMA) micelles could effectively deliver and release DOX in human breast cancer cell line (MCF-7 cells). MTT assay showed that dextran-g-P(DPA-co-TIBMA) exhibited excellent biocompatibility while DOX-loaded dextran-g-P(DPA-co-TIBMA) micelles have good antitumor efficacy in vitro. The in vivo therapeutic studies indicated that the DOX-loaded dextran-g-P(PDPA-co-TIBMA) micelles could effectively reduce the growth of tumor with little body weight reduction.

High-Density Three-Dimensional Network of Covalently Linked Nitric Oxide Donors to Achieve Antibacterial and Antibiofilm Surfaces.

Bacterial colonization on biomedical devices often leads to biofilms that are recalcitrant to antibiotic treatment and the leading cause of hospital-acquired infections. We have invented a novel pretreatment chemistry for device surfaces to produce a high-density three-dimensional (3-D) network of covalently linked S-nitrosothiol (RSNO), which is a nitric oxide (NO) donor. Poly(polyethylene glycol-hydroxyl-terminated) (i.e., PPEG-OH) brushes were grafted from an ozone-pretreated polyurethane (PU) surface. The high-density hydroxyl groups on the dangling PPEG-OH brushes then underwent condensation with a mercapto-silane (i.e., MPS, mercaptopropyl trimethoxysilane) followed by S-nitrosylation to produce a 3-D network of NO-releasing RSNO to form the PU/PPEG-OH-MPS-NO coating. This 3-D coating produces NO flux of up to 7 nmol/(cm2 min), which is nearly 3 orders of magnitude higher than the picomole/(cm2 min) levels of other NO-releasing biomedical implants previously reported. The covalent immobilization of RSNO avoids donor leaching and reduces the risks of cytotoxicity arising from leachable RSNO. Our coated PU surfaces display good biocompatibility and exhibit excellent antibiofilm formation activity in vitro (up to 99.99%) against a broad spectrum of Gram-positive and Gram-negative bacteria. Further, the high-density RSNO achieves nearly 99% and 99.9% in vivo reduction of Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) in a murine subcutaneous implantation infection model. Our surface chemistry to create high NO payload without NO-donor leaching can be applied to many biomedical devices.

Mussel Adhesive Mimetic Silk Sericin Prepared by Enzymatic Oxidation for the Construction of Antibacterial Coatings.

With the rapid development and advancement in orthodontic and orthopedic technologies, the demand for biomedical-grade titanium (Ti) alloys is growing. The Ti-based implants are susceptible to bacterial infections, leading to poor healing and osteointegration, resulting in implant failure or repeated surgical intervention. Silk sericin (SS) is hydrophilic, biocompatible, and biodegradable and could induce a low immunological response in vivo. As a result, it would be intriguing to investigate the use of hydrophilic SS in surface modification. In this work, the tyrosine moiety in SS was oxidized by tyrosinase (or polyphenol oxidase) to the 3,4-dihydroxyphenylalanine (DOPA) form, generating the catechol moiety-containing SS (SSC). Inspired by the adhesion of mussel foot proteins, the SSC coatings could be directly deposited onto multiple surfaces in SS and tyrosinase mixed stock solutions to create active surfaces with catechol groups. Further, the SSC-coated Ti surfaces were hybridized with silver nanoparticles (Ag NPs) via in situ silver ion (Ag+) reduction. The antibacterial properties of the Ag NPs/SS-coated Ti surfaces are demonstrated, and they can prevent bacterial cell adhesion as well as early-stage biofilm formation. In addition, the developed Ag NPs/SSC-coated Ti surfaces exhibited a negligible level of cytotoxicity in L929 mouse fibroblast cells.

UV-Assisted Deposition of Antibacterial Ag-Tannic Acid Nanocomposite Coating.

The marked increase in bacterial colonization of medical devices and multiple drug resistance to traditional antibiotics underline the pressing need for developing novel antibacterial surface coatings. In the present investigation, natural polyphenol tannic acid (TA)-capped silver nanoparticles (TA-Ag NPs) were synthesized via an environmentally friendly and sustainable one-step redox reaction under UV irradiation with a simultaneous and uniform deposition on polydimethylsiloxane (PDMS) and other substrate surfaces. In the synthesis process, the dihydroxyphenyl and trihydroxyphenyl groups of TA actively participate in Ag+ reduction, forming co-ordination linkages with Ag NPs and bestowing the deposition on the PDMS surface. The physico-chemical features of TA-Ag NPs were characterized in detail. Microscopic examination, surface elemental analysis, and wettability measurements clearly reveal the decoration of TA-Ag NPs on the substrate surfaces. The modified PDMS surfaces can kill the adhered bacteria or resist the bacterial adhesion, and no live bacteria can be found on their surfaces. Most importantly, the modified PDMS surfaces exhibit predominant antibacterial effects both in vitro in the catheter bridge model and in vivo in a rat subcutaneous infection model. On the other hand, the functionalized surfaces exhibit only a negligible level of cytotoxicity against L929 mouse fibroblasts with no side effects on the major organs of Sprague-Dawley rats after implantation, indicating their biocompatibility for potential biomedical applications.

Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating.

Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.

Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications.

New generation antimicrobial agents are expected to exhibit non-metabolic killing mechanisms, high killing potency and biocompatibility. We synthesized a cationic chitosan derivative and an anionic chitosan derivative - specifically an α-poly(l)lysine side-grafted chitosan (CS-PLL) and an anionic citraconyl anhydride (CA) modified polylysine side graft for chitosan (CS-PLL-CA). The ß-carboxylic amide of CS-PLL-CA is pH-labile and self-cleavable under pH 6 or below. When we mixed the cationic (CS-PLL) and anionic (CS-PLL-CA) peptidosaccharide copolymers, they self-assembled, due to electrostatic charge interactions, into nanomicelles (NMs) with the oppositely charged peptides in the core and the chitosan polysaccharide arms on the shell. The NMs exhibited high hemo- and cytocompatibility (nontoxic) at physiological pH of 7.4, due to the chitosan protection on the shell and charge neutralization on the core. Upon reaching the bacterial infection site, the chitosan shell interacted and accumulated around the bacteria. The bacterial infection sites in the body usually show localized acidity as a result of the combined actions of bacterial metabolism and host immune response, and the pH can decrease to as low as 5.5. At this low pH, the ß-carboxylic amide bond of the anionic polypeptide gradually hydrolyzed to expose the initial cationic amine moieties, causing the NMs to 'decompose' into individual CS-PLL and 'spill' the cationic molecules which then disrupted and killed the bacteria. This 'smart' bacteria-recognizing chitosan-decorated nanosystem opens the pathway to explore other anionic and cationic and biocompatible polymers for 'stealth' delivery of antimicrobial polypeptide, and 'on-demand' recovery of the cationic parts to kill bacteria at infection sites.

Nontoxic Antimicrobial Cationic Peptide Nanoconstructs with Bacteria-Displaceable Polymeric Counteranions.

Antimicrobial peptides that target the integrity of bacterial envelopes can eradicate pathogens with little development of resistance, but they often inflict nonselective toxicity toward mammalian cells. The prevailing approach to optimize the selectivity of cationic peptides has been to modify their composition. Instead, we invent a new generation of broad-spectrum antibacterial nanoconstructs with negligible mammalian cell toxicity through a competitive displacement of counter polyanions from the complementary polycations. The nanoconstruct, which has a highly cationic Au nanoparticles (NPs) core shielded by polymeric counterions, is inert in nonbacterial environments. When exposed to negatively charged bacterial envelopes, this construct sheds its polyanions, triggering a cationic Au NP/bacterial membrane interaction that rapidly kills Gram-positive and Gram-negative bacteria. The anionic charge and hydrophilicity of the polyanion provides charge neutralization for the peptide-decorated Au NP core, but it is also bacteria-displaceable. These results provide a foundation for the development of other cationic particles and polymeric counterion combinations with potent antimicrobial activity without toxicity.