No abstract

The development of effective cancer vaccines is an important direction in the area of cancer immunotherapy. Although certain types of preventive cancer vaccines have already been used in the clinic, therapeutic cancer vaccines for treatment of already established tumors are still in high demand. In this study, we develop a new type of cancer vaccine by mixing cellpenetrating peptide (CPP) conjugated antigen as the enhanced antigen, together with CpG as the immune adjuvant. A special CPP, cytosol-localizing internalization peptide 6 (CLIP6), which has the ability to enter cells exclusively via a nonendosomal mechanism, i.e., direct translocation across the cell membrane, is conjugated with model antigen ovalbumin (OVA). Compared to naked OVA, the obtained CLIP6-OVA conjugates show greatly increased uptake by dendritic cells (DCs) and, more importantly, remarkably enhanced antigen cross-presentation, eliciting stronger cytotoxic T lymphocyte (CTL) mediated immune responses with the help of CpG. This CLIP6-OVA/CpG formulation offers effective protection for mice against challenged B16-OVA tumors, and is able to further function as a therapeutic vaccine, which, in combination with immune checkpoint blockade therapy, can significantly suppress the alreadyestablished tumors. Such a CLIP6-based cancer vaccine developing strategy shows promising potential toward clinical practice owing to its features of easy preparation, low cost, and remarkable biocompatibility.

The spread of antibiotic-resistance poses a great threat, making it a growing need to develop other antibacterial strategies and therapeutics. Recently, owing to their excellent physicochemical properties, copper chalcogenides have received extensive attention as photothermal agents. However, most reports are focused on Cu 2−x S nanoparticles, whereas very few water-dispersible Cu 2−x Se nanomaterials have been reported due to their difficult preparation process. Herein, water-dispersible and biocompatible cuprous selenide nanosheets (Cu 2 Se NSs) were synthesized by a simple anion exchange method starting from cuprous oxide nanorods (Cu 2 O NRs), which could also help avoid any environmental pollution caused by the organic solvent used during synthesis. The obtained Cu 2 Se NSs showed strong absorption in the second near-infrared window (NIR II) with a good photothermal conversion efficiency as high as ∼61.16%, outstanding among the previously reported NIR II photothermal agents. Interestingly, using Staphylococcus aureus and Escherichia coli as model pathogens, these Cu 2 Se NSs possess an intrinsic bacteriostatic effect and could inhibit the growth of both bacteria species. Furthermore, both the fluorescent-based microscopy and the bacterial morphology analysis using a scanning electron microscope have demonstrated that incubation of both species of bacteria with Cu 2 Se NSs under laser irradiation (1064 nm) would lead to complete disruption of the bacterial cell wall. Our work presents a facile method to prepare water-dispersible Cu 2 Se NSs-, which could serve as highly efficient dual-functional antibacterial agents.