Facile preparation of a metal-phenolic network-based lymph node targeting nanovaccine for antitumor immunotherapy.

Cancer vaccines are being explored for enhanced cancer immunotherapy and prophylaxis. Some of their prevailing weaknesses, however, such as complicated preparation, poor biocompatibility, and failure to elicit strong cellular immune responses, have limited their further clinical applications. Here, we reported a multifunctional nanovaccine that was prepared in a quick and simple way. During the self-assembly of metal-phenolic networks (MPNs), the antigen ovalbumin (OVA) and immunoreactive chlorogenic acid (CHA) were simultaneously loaded. Owing to its dual pH and reduction sensitivities, the nanovaccine could deliver antigens into the cytoplasm of dendritic cells (DCs) and facilitate the cross-presentation of antigens. Moreover, the results of in vivo immunization assays demonstrated that the nanovaccine significantly excited the antigen presentation of DCs and provoked a robust cellular immune response with the restrained activation of regulatory T cells (Tregs), by targeting lymph nodes and executing the function of CHA. In vivo antitumor assays indicated that the nanovaccine with good biocompatibility afforded conspicuous cancer treatment and prevention effects. Overall, the nanovaccine presented in this study shows a promise for potentiating cancer immunotherapy by the lymph node-targeted delivery. STATEMENT OF SIGNIFICANCE: Cancer nanovaccines can be used for cancer immunotherapy. However, some existing shortcomings, such as cumbersome preparation, poor biocompatibility, and failure to elicit strong immune responses, limit the clinical application of cancer nanovaccines. This study developed a multifunctional nanovaccine that was readily prepared through the self-assembly of metal-phenolic networks. The nanovaccine with dual pH and reduction sensitivities could efficiently promote the antigen lysosome escape and cross-presentation. In vivo, it efficiently delivered antigen into lymph nodes and provoked strong cellular immune responses, and thus it showed significant cancer immunotherapy and prevention effect.

CEO Relational Leadership and Product Innovation Performance: The Roles of TMT Behavior and Characteristics.

CEO leadership is considered a critical antecedent of product innovation performance, but the relational aspect of leadership has been largely neglected in this area. Drawing on upper echelons theory and relational leadership literature, this study explores whether, how, and when CEO relational leadership influences product innovation performance. Specifically, we analyze the underlying mechanism of TMT (top management team) voice behavior and two boundary conditions-TMT educational level and TMT age. Based on multi-source and multi-wave data on 105 Chinese firms, this study finds that CEO relational leadership plays an important role in promoting product innovation performance through the intervening mechanism of TMT voice behavior. Furthermore, the positive relationship between CEO relational leadership and TMT voice behavior is stronger in TMTs with higher educational level and lower age. This study contributes to the existing literature by empirically examining the under-investigated relationship between CEO relational leadership and product innovation performance, and by disentangling the underlying mechanism and boundary conditions.

Metal-Phenolic Network-Encapsulated Nanovaccine with pH and Reduction Dual Responsiveness for Enhanced Cancer Immunotherapy.

Cancer nanovaccines have been widely explored to enhance immunotherapy efficiency, in which the significant irritation of antigen-specific cytotoxic T cells (CTLs) is the critical point. In this study, we developed a pH and reduction dual-sensitive nanovaccine (PMSN@OVA-MPN) composed of two parts. The inner part was made up of polyethyleneimine (PEI)-modified mesoporous silica nanoparticles (MSNs) loaded with model antigen ovalbumin (OVA) and the outer part was made up of disulfide bond-involved metal-phenolic networks (MPNs) as a protective corona. In vitro release experiments proved that PMSN@OVA-MPN could intelligently release OVA in the presence of reductive glutathione, but not in neutral phosphate-buffered saline (PBS). Moreover, in vitro cell assays indicated that the nanovaccine promoted not only the OVA uptake efficiency by DC2.4 cells but also antigen lysosome escape due to the proton sponge effect of PEI. Furthermore, in vivo animal experiments indicated that PMSN@OVA-MPN induced a large tumor-specific cellular immune response so as to effectively inhibit the growth of an existing tumor. Finally, the immune memory effect caused by the nanovaccine afforded conspicuous prophylaxis efficacy in neonatal tumors. Hence, the multifunctional vaccine delivery system prepared in this work exhibits a great application potential in cancer immunotherapy and offers a platform for the development of nanovaccines.