Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer.

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Secondary Amine Pendant ß-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking ß-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial ß-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.

Practical Preparation of Infection-Resistant Biomedical Surfaces from Antimicrobial ß-Peptide Polymers.

Tackling microbial infection associated with biomaterial surfaces has been an urgent need. Synthetic ß-peptide polymers can mimic host defense peptides and have potent antimicrobial activities without driving the bacteria to develop antimicrobial resistance. Herein, we demonstrate a plasma surface activation-based practical ß-peptide polymer modification to prepare antimicrobial surfaces for biomedical materials such as thermoplastic polyurethane (TPU), polytetrafluoroethylene, polyvinyl pyrrolidone, polyvinyl chloride, and polydimethylsiloxane. The ß-peptide polymer-modified surfaces demonstrated effective killing on drug-resistant Gram-positive and Gram-negative bacteria. The antibacterial function retained completely even after the ß-peptide polymer-modified surfaces were stored at ambient temperature for at least 2 months. Moreover, the optimum ß-peptide polymer (50:50 DM-Hex)-modified surfaces displayed no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA)-pre-incubated TPU-50:50 DM-Hex surfaces for subcutaneous implantation revealed a 3.4-log reduction of MRSA cells after the implantation for 11 days at the surrounding tissue of implanted TPU sheet and significant suppression of infection, compared to bare TPU control. These results imply promising and practical applications of ß-peptide polymer tethering to prepare infection-resistant surfaces for biomedical materials and devices.