Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating Copolymers for Bone Repair.

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 µg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 µg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the growth-factor-encapsulated antibacterial vesicles have better bone repair ability compared with control groups without antibacterial vesicles. Overall, we have provided a novel method for designing PMAC-based highly effective intrinsically antibacterial vesicles that may have promising biomedical applications in the future.

Multifunctional biocompatible and biodegradable folic acid conjugated poly(ε-caprolactone)-polypeptide copolymer vesicles with excellent antibacterial activities.

Cancer patients after chemotherapy may also suffer bacterial attack due to badly decreased immunity. Although with high bacterial efficacy, conventional antibiotics are prone to inducement of drug resistance and may be not suitable for some cancer patients. In contrast, antibacterial peptides are highly effective in inhibiting bacteria without inducing resistance in pathogens. Presented in this article is a novel kind of highly effective antibacterial peptide-based biocompatible and biodegradable block copolymer vesicle. The copolymer is poly(ε-caprolactone)-block-poly[phenylalanine-stat-lysine-stat-(lysine-folic acid)] [PCL19-b-poly[Phe12-stat-Lys9-stat-(Lys-FA)6]], which can self-assemble into vesicles in aqueous solution. The biocompatible and biodegradable PCL forms the vesicle membrane, whereas the poly[Phe12-stat-Lys9-stat-(Lys-FA)6] block constitutes the vesicle coronas. Compared to the individual polymer chains, the vesicles showed enhanced antibacterial activities against both Gram-positive and Gram-negative bacteria (16 µg mL(-1)) due to the locally concentrated antibacterial poly[Phe12-stat-Lys9-stat-(Lys-FA)6] coronas, which may avoid the inducement of antibiotic-resistant bacteria and side effects of multidrug interactions. Furthermore, folic acid is introduced into the vesicle coronas for potential further applications such as cancer-targeted drug delivery. Moreover, the amino groups can be further functionalized when necessary. This low cytotoxic, biocompatible, biodegradable, and antibacterial vesicle (without antibiotic resistance) may benefit patients after tumor surgery because it is highly anti-inflammatory, and it is possible to deliver the anticancer drug to tumor cells simultaneously.

Coal utilization in China: environmental impacts and human health.

Coal is one of the major energy resources in China, accounting for approximately 70 % of primary energy consumption. Many environmental problems and human health risks arise during coal exploitation, utilization, and waste disposal, especially in the remote mountainous areas of western China (e.g., eastern Yunnan, western Guizhou and Hubei, and southern Shaanxi). In this paper, we report a thorough review of the environmental and human health impacts related to coal utilization in China. The abundance of the toxic trace elements such as F, As, Se, and Hg in Chinese coals is summarized. The environmental problems (i.e., water, soil, and air pollution) that are related to coal utilization are outlined. The provenance, distributions, typical symptoms, sources, and possible pathways of endemic fluorosis, arsenism, and selenosis due to improper coal usage (briquettes mixed with high-F clay, mineralized As-rich coal, and Se-rich stone coal) are discussed in detail. In 2010, 14.8, 1.9 million, and 16,000 Chinese people suffered from dental fluorosis, skeletal fluorosis, and arsenism, respectively. Finally, several suggestions are proposed for the prevention and treatment for endemic problems caused by coal utilization.

Mimics of Host Defense Peptides Derived from Dendronized Polylysines for Antibacterial and Anticancer Therapy.

Bacteria in tumor microenvironments promote carcinogenesis and trigger complications, suggesting the significance of intervening in bacterial growth in cancer treatment. Here, dendrimer-derived mimics (DMs) of host defense peptides (HDPs) were designed for antibacterial and anticancer therapy, which feature a dendronized polylysine core and polycaprolactone arms. DMs displayed not only remarkable activities against Staphylococcus aureus and human lung cancer cells, but also exceptional selectivity. The membranolytic mechanism revealed by morphology analysis explained their low susceptibility to induce resistance. Further, the optimized DM inhibited tumor growth in the subcutaneous tumor model when administered via intraperitoneal injection and exhibited negligible toxicity to tissues. Overall, we combined the superiority of dendrimers and the mechanism from HDPs to design agents with dual antibacterial and anticancer activities that possess great potential for clinical oncology therapy.

A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability.

Despite advanced sterilization and aseptic techniques, infections associated with medical implants have not been eradicated. Most present coatings cannot simultaneously fulfil the requirements of antibacterial and antifungal activity as well as biocompatibility and reusability. Here, we report an antimicrobial hydrogel based on dimethyldecylammonium chitosan (with high quaternization)-graft-poly(ethylene glycol) methacrylate (DMDC-Q-g-EM) and poly(ethylene glycol) diacrylate, which has excellent antimicrobial efficacy against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Fusarium solani. The proposed mechanism of the antimicrobial activity of the polycationic hydrogel is by attraction of sections of anionic microbial membrane into the internal nanopores of the hydrogel, like an 'anion sponge', leading to microbial membrane disruption and then microbe death. We have also demonstrated a thin uniform adherent coating of the hydrogel by simple ultraviolet immobilization. An animal study shows that DMDC-Q-g-EM hydrogel coating is biocompatible with rabbit conjunctiva and has no toxicity to the epithelial cells or the underlying stroma.

High potency and broad-spectrum antimicrobial peptides synthesized via ring-opening polymerization of alpha-aminoacid-N-carboxyanhydrides.

Antimicrobial peptides (AMPs), particularly those effective against methicillin-resistant Staphylococcus aureus ( S. aureus ) and antibiotic-resistant Pseudomonas aeruginosa ( P. aeruginosa ), are important alternatives to antibiotics. Typical peptide synthesis methods involving solid-phase sequential synthesis are slow and costly, which are obstacles to their more widespread application. In this paper, we synthesize peptides via ring-opening polymerization of alpha-amino acid N-carboxyanhydrides (NCA) using a transition metal initiator. This method offers high potential for inexpensive synthesis of substantial quantities of AMPs. Lysine (K) was chosen as the hydrophilic amino acid and alanine (A), phenylalanine (F), and leucine (L) as the hydrophobic amino acids. We synthesized five series of AMPs (i.e., P(KA), P(KL), P(KF), P(KAL), and P(KFL)), varied the hydrophobic amino acid content from 0 to 100%, and determined minimal inhibitory concentrations (MICs) against clinically important Gram-negative and Gram-positive bacteria and fungi (i.e., Escherichia coli ( E. coli ), P. aeruginosa , Serratia marcescens ( S. marcescens ), and Candida albicans ( C. albicans ). We found that P(K(10)F(7.5)L(7.5)) and P(K(10)F(15)) show the broadest activity against all five pathogens and have the lowest MICs against these pathogens. For P(K(10)F(7.5)L(7.5)), the MICs against E. coli , P. aeruginosa , S. marcescens , S. aureus , and C. albicans are 31 microg/mL, 31 microg/mL, 250 microg/mL, 31 microg/mL, and 62.5 microg/mL, while for P(K(10)F(15)) the respective MICs are 31 microg/mL, 31 microg/mL, 250 microg/mL, 31 microg/mL, and 125 microg/mL. These are lower than the MICs of many naturally occurring AMPs. The membrane depolarization and SEM assays confirm that the mechanism of microbe killing by P(K(10)F(7.5)L(7.5)) copeptide includes membrane disruption, which is likely to inhibit rapid induction of AMP-resistance in pathogens.

High water content hydrogel with super high refractive index.

Transparent, high water content (>65%), and cytocompatible hydrogels, which also possess super high refractive indices (RI > 1.5), are needed for ophthalmological applications. Most hydrogels can achieve either high RI or high water content but not both in the same system because water is a low RI material. Here, high water content/high RI hydrogels fabricated through elevated-temperature UV polymerization of an aqueous solution of acrylamide (AM) and methacrylamide (MAM) with tri(ethylene glycol) dimethacrylate (TEDA) crosslinker are reported. By varying the AM:MAM ratios (2:8 to 8:2) and crosslinker density (5 to 11 mol %), it is discovered that high water content (66%) AM:MAM copolymer hydrogels exhibiting anomalously high refractive indices (1.53); they are also colorless, transparent (99.4%), and cytocompatible with human keratinocytes.

A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-L-lysine.

Hydrogels made from epsilon-poly-l-lysine-graft-methacrylamide (EPL-MA) have been found to have impressive wide spectrum antimicrobial activity against both bacteria (specifically Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus) and fungi (specifically Candida albicans and Fusarium solani). The EPL-MA hydrogel also possesses in vitro biocompatibility and EPL-MA solution is relatively non-hemolytic: the concentration needed for onset of human red blood cell (hRBC) hemolysis is 12,500 µg/mL so that the selectivity for the pathogenic microorganisms over hRBCs is 230-1560. Further, EPL-MA hydrogel can be conveniently ultraviolet-immobilized onto plasma-treated plastic surfaces to form thin highly adherent antimicrobial hydrogel coatings for medical devices and implants.

Synthesis and characterization of multiblock copolymers based on spider dragline silk proteins.

Spider dragline silk with its superlative tensile properties provides an ideal system to study the relationship between morphology and mechanical properties of a structural protein. Accordingly, we synthesized two hybrid multiblock copolymers by condensing poly(alanine) [(Ala)(5)] blocks of the structural proteins (spidroin MaSp1 and MaSp2) of spider dragline silk with different oligomers of isoprene (2200 and 5000 Da) having reactive end groups. The synthetic multiblock polymer displayed similar secondary structure to that of natural spidroin, the peptide segment forming a beta-sheet structure. These multiblock polymers showed a significant solubility in the component solvents. Moreover, the copolymer which contains the short polyisoprene segment would aggregate into a micellar-like structure, as observed by TEM.