Search

A multifunctional natural polyphenol-functionalized chitosan/gelatin sponge (PCGS) is reported for hemostatic and infected wound therapy.

The combination of photothermal therapy (PTT) and gene therapy (GT) has attracted intense interest in cancer treatment. However, the lack of long circulation and active tumor targeting reduces the therapeutic efficacy of complementary PTT/GT. In this work, hyaluronic acid (HA)-cloaked gold nanorods-PGED (prepared by ring-opening of polyglycidyl methacrylate (PGMA) with ethylenediamine (ED))/pDNA (AP/pDNA-HA) complexes were prepared to achieve long circulation and tumor targeting for photoacoustic imaging (PAI)-guided synergistic PTT/GT. Gold nanorods endow the complexes with photothermal effect and PAI function. Benefiting from the HA cloak, the AP/pDNA-HA complexes exhibit excellent stability, biocompatibility, long circulation behavior and active targeting. In addition, the pH-responsive characteristic of the Schiff base bonds helps the AP/pDNA-HA complexes to effectively escape from the endosome/lysosome. The antioncogene p53 was employed to investigate the gene transfection efficiency of the delivery system both

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology is a promising approach for cancer therapy, and its application practice urgently requires a safe and effective gene carrier. In this work, we focus on the design of a phenylboronic acid (PBA)-functionalized, disulfide bonded branched polyaminoglycoside (SS-HPT-P) as a robust delivery vector of the CRISPR-Cas9 system. SS-HPT-P showed great tumor-targeting performance, reduction-responsive degradability, and gene transfection ability. The typical pCas9-surv (one CRISPR-Cas9 plasmid that targets and knocks out the survivin gene) delivery mediated by SS-HPT-P exhibited gene editing performance in the A549 cell line, confirming the feasibility of SS-HPT-P to effectively deliver the CRISPR-Cas9 system. SS-HPT-P/pCas9-surv could effectively inhibit the proliferation of tumor cells both in vitro and in vivo, suggesting the potential of PBA-functionalized nanocarriers for cancer gene therapy. The present work provides a promising approach for the treatment of malignant tumors.

Skin, the largest organ in the human body, provides several important functions, including providing protection from mechanical impacts, micro-organisms, radiation and chemicals; regulation of body temperature; the sensations of touch and temperature; and the synthesis of several substances including vitamin D, melanin, and keratin. Common dermatological disorders (CDDs) include inflammatory or immune-mediated skin diseases, skin infection, skin cancer, and wounds. In the treatment of skin disorders, topical administration has advantages over other routes of administration, and polymers are widely used as vehicles to facilitate the delivery of topical therapeutic agents, serving as matrices to keep therapeutic agents in contact with the skin. Nitric oxide (NO), a cellular signalling molecule, has attracted significant interest in treating a broad spectrum of diseases, including various skin disorders. However, there are a number of challenges in effectively delivering NO. It must be delivered in a controlled manner at sufficient concentrations to be efficacious and the delivery system must be stable during storage. The use of polymer-based systems to deliver NO topically can be an effective strategy to overcome these challenges. There are three main approaches for incorporating NO with polymers in topical delivery systems: (i) physical incorporation of NO donors into polymer bases; (ii) covalent attachment of NO donors to polymers; and (iii) encapsulation of NO donors in polymer-based particles. The latter two approaches provide the greatest control over NO release and have been used by numerous researchers in treating CDDs, including chronic wounds and skin cancer.

Catheter-induced infection is a severe problem in clinical practice, which induces significant morbidity, mortality and treatment costs. Therefore, there is a great requirement for developing antibacterial surfaces of catheter materials. In the present study, we develop a strategy for constructing self-adaptive antibacterial surfaces with bacterium-triggered antifouling-bactericidal switching properties on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer coating with one hierarchical structure was readily constructed on the PU surface (PU-PQ-PEG), which was composed of poly[2-(dimethyl decyl ammonium)ethyl methacrylate] (PQDMAEMA) brushes as the bactericidal lower layer and polyethylene glycol (PEG) as the antifouling upper layer. The two layers were incorporated with Schiff base structures, which could be broken by the metabolism of bacteria. Under normal and mild infection conditions, PU-PQ-PEG showed excellent antifouling and biocompatible properties against proteins and bacteria. When serious infection occurred and bacteria colonized on the PU-PQ-PEG surface, the bacteria could trigger the self-adaptive antifouling-bactericidal switching of the surface. Furthermore, the self-adaptive antibacterial properties of PU-PQ-PEG were also confirmed by an in vitro circulating model to simulate hydrodynamic conditions. PU-PQ-PEG showed self-adaptive antibacterial performances both under static and hydrodynamic conditions. The results of animal experiments also demonstrated the in vivo anti-infection performance. The present work will provide a promising strategy for developing antibacterial surfaces of catheter materials with hemocompatibility.

The design of novel antibacterial materials has attracted increasing attention for combating bacterial infections. Herein, we conjugated zinc(ii) monoamino phthalocyanine (ZnMAPc) to poly(glycidyl methacrylate) (PGMA) via a ring-opening reaction, and the excess epoxy groups were scavenged by ethylenediamine (ED). The resultant macro-photosensitizer (PGED-Pc) can be easily dispersed in aqueous solution to form self-assembled nanoparticles and generate reactive oxygen species for inactivation of bacteria when exposed to light illumination. We found that the photodynamic pathway for the generation of singlet oxygen (1O2) was strongly inhibited in aqueous solution, and the major components for the inactivation of bacteria were superoxide anion radicals (˙O2-) and hydrogen peroxide (H2O2), which could result in the disruption of bacterial envelopes, the inactivation of vital enzymes, and the degradation of genomic DNA. PGED-Pc exhibited potent photodynamic antibacterial activity, with minimum bactericidal concentration (MBC, defined as 99.9% inactivation of bacteria) values of 128 μg mL-1 for Escherichia coli (E. coli) and 4 μg mL-1 for Staphylococcus aureus (S. aureus). As a proof-of-concept, the PGED-Pc nano-assemblies in aqueous solution can be readily immobilized on glass slides via a Schiff-base reaction, and impose potent photodynamic antibacterial activity upon light illumination. This work unveils a promising strategy for the engineering of self-sterilizing surfaces to combat bacterial infections.

Among various polymeric gene delivery systems, peptide-based vectors demonstrate great potential owing to their unique structure and properties, including flexibility; however, there is insufficient molecular understanding of the role and properties of amino acids as building blocks in gene delivery. In this work, we constructed a series of histidine (H)-containing peptide-grafted dextran (D-RxHy) vectors via a simple two-step reaction of dextran with five RxHyC peptides: R7H3C, R5H3C, R5H5C, R3H5C, and R3H7C. The gel electrophoresis study unveiled the DNA-binding ability of H residues. While all D-RxHy vectors possess similarly low cytotoxicity, D-R3H7 exhibited the highest gene transfection efficiency. Interestingly, at the low nitrogen to phosphate (N/P) ratio of 2, D-R3H7 displayed a 6–8-fold higher luciferase expression compared to the gold standard branched PEI (25k). D-R3H7 and D-R5H5 demonstrated favorable cell uptake rates. A chloroquine-treated transfection assay confirmed the key effect of the high buffering capacity of H-rich D-R3H7 on its high gene transfection efficiency, especially at low N/P ratios. The present work unveiled that histidine is critical for both DNA condensation and the accurate control of endosomal escape. The tunable D-RxHy platform not only demonstrates promising potential for therapeutic purposes but can also be used as a tool to elucidate the molecular mechanism of polymer-based transfection.

Lipids, as the greatest constituent in cell membranes, have been widely used for biomedical applications because of their excellent biological properties. The introduction of membrane lipid molecules into gene vectors would embody greater biocompatibility, cellular uptake and transfection efficiency. In this work, one flexible strategy for readily conjugating lipid molecules with polycations was proposed based on atom transfer radical polymerization to produce a series of cholesterol (CHO)- and phosphatidylinositol (PI)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s, namely CHO-PGEAs and PI-PGEAs, as effective gene carriers. CHO-PGEAs and PI-PGEAs truly demonstrated much better transfection performances compared to linear ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) counterparts and traditional standard branched polythylenimine (PEI, 25 kDa). In addition, the good antitumor effects of CHO-PGEA and PI-PGEA were confirmed with suppressor tumor gene p53 systems in vitro and in vivo. The present work could provide a new strategy to develop effective cationic conjugation of lipid molecules for gene therapy.