RESUMEN
Despite recent advancements of sonodynamic therapy (SDT) in cancer immunotherapy, challenges have yet to be surmounted to further boost its immunotherapeutic efficacy due to the low-level tumor antigens presentation of dendritic cells (DCs). Cell membrane camouflaged-nanoparticles can integrate the neoantigens of the cancer cell membrane with the multifunctionalities of synthetic nanocores. Herein, sono-responsive nanoparticles coated with DC-targeted antibody chimeric cancer cell membrane are investigated for multimodal therapy. The nanometal organic frameworks (MOFs) that respond to ultrasound are loaded successfully inside the vesicles displaying an anti-DEC205 antibody. The anti-DEC205 chimeric vesicles can directly target and activate DCs, promote tumor antigens cross-presentation, and then produce a cascade amplified T-cell immune response. Upon deep tissue-penetrating sonication, AMR-MOF@AuPt generates large amounts of reactive oxygen species that directly kill cancer cells, further initiating an anti-cancer T cell immune response. Such synergistic sono-immunotherapies effectually inhibit tumor growth and induce strong systemic and long-term immune memory against cancer recurrence and distant metastasis. The authors findings provide DCs and tumor cells of a dual active-targeting cell membrane-coated sono-immunotherapeutic nanoplatform for cancer therapy.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Células Dendríticas/metabolismo , Inmunoterapia , Antígenos de Neoplasias , Linfocitos T/metabolismo , Neoplasias/metabolismo , Línea Celular TumoralRESUMEN
PURPOSE: To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. METHODS: In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. RESULTS: SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. CONCLUSION: Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.
Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Nanopartículas , Cirugía Asistida por Computador , Animales , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Aceite Etiodizado , Humanos , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen Óptica/métodos , Conejos , Cirugía Asistida por Computador/métodosRESUMEN
Simplifying the manufacturing processes of multilayered high-performance perovskite solar cells (PSCs) is yet of vital importance for their cost-effective production. Herein, an in situ blending strategy is presented for co-deposition of electron transport layer (ETL) and perovskite absorber by incorporating (3-(7-butyl-1,3,6,8-tetraoxo-3,6,7,8-tetrahydrobenzo- [lmn][3,8]phenanthrolin-2(1H)-yl)propyl)phosphonic acid (NDP) into the perovskite precursor solutions. The phosphonic acid-like anchoring group coupled with its large molecular size drives the migration of NDP toward indium tin oxide (ITO) surface to form a distinct ETL during perovskite film forming. This strategy circumvents the critical wetting issue and simultaneously improves the interfacial charge collection efficiencies. Consequently, n-i-p PSCs based on in situ blended NDP achieve a champion power conversion efficiency (PCE) of 24.01%, which is one of the highest values for PSCs using organic ETLs. This performance is notably higher than that of ETL-free (21.19%) and independently spin-coated (21.42%) counterparts. More encouragingly, the in situ blending strategy dramatically enhances the device stability under harsh conditions by retaining over 90% of initial efficiencies after 250 h in 100 °C or 65% humidity storage. Moreover, this strategy is universally adaptable to various perovskite compositions, device architectures, and electron transport materials (ETMs), showing great potential for applications in diverse optoelectronic devices.
RESUMEN
Naphthalene diimides (NDI) are widely serving as the skeleton to construct electron transport materials (ETMs) for optoelectronic devices. However, most of the reported NDI-based ETMs suffer from poor interfaces with the perovskite which deteriorates the carrier extraction and device stability. Here, a representative design concept for editing the peripheral groups of NDI molecules to achieve multifunctional properties is introduced. The resulting molecule 2,7-bis(2,2,3,3,4,4,4-heptafluorobutyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-C4F) incorporated with hydrophobic fluorine units contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability and the formation of strong chemical coordination with perovskite precursors. All these features favor retarding the perovskite crystallization and achieving superior buried interfaces, which subsequently promote charge collection and improve the structural compatibility between perovskite and ETMs. The corresponding PSCs based on low-temperature processed NDI-C4F yield a record efficiency of 23.21%, which is the highest reported value for organic ETMs in n-i-p PSCs. More encouragingly, the unencapsulated devices with NDI-C4F demonstrate extraordinary stability by retaining over 90% of their initial PCEs after 2600 h in air. This work provides an alternative molecular strategy to engineer the buried interfaces and can trigger further development of organic ETMs toward reliable PSCs.
RESUMEN
Current oxidative stress amplifying strategies for immunogenic cell death (ICD) promotion are mainly restricted to immune tolerance induced by adaptive cellular antioxidation, limited tumor-selectivity, and tumoral immunosuppression. Herein, a facile and efficient scenario of genetically engineering transferrin-expressing cell membrane nanovesicle encapsulated IR820-dihydroartemisinin nanomedicine (Tf@IR820-DHA) was developed to boost a-PD-L1-mediated immune checkpoint blocking (ICB) via synergetic triple stimuli-activated oxidative stress-associated ICD. We demonstrate that the engineered transferrin of Tf@IR820-DHA has excellent tumor targeting and Fe(III)-loading properties and thus delivered Fe(III) and IR820-DHA nanoparticles (NPs) to the lesion location effectively. We found that the self-carrying Fe(III)-mediated programmable catalysis of DHA and glutathione (GSH) depletion generated plenty of reactive oxygen species (ROS). Moreover, DHA also acted as an immunomodulator to decrease the number of T regulatory cells, thereby remodeling the tumor immune microenvironment and achieving double T cell activation. Furthermore, the IR820 molecule served as a competent sonosensitizer to produce ROS under ultrasound activation and guide precise immunotherapy via fluorescent/photoacoustic (FL/PA) imaging. Through its three-pronged delivery of stimuli-activated oxidative stress (DHA-induced chemodynamic therapy, catalysis-conferred GSH depletion, and IR820-mediated sonodynamic therapy), Tf@IR820-DHA caused high levels of targeted ICD. This significantly increased the proportions of IFN-γ-secreting T cells (CD4+ T and CD8+ T) and enhanced a-PD-L1-mediated ICB against primary and distant tumors, which represents a promising approach for cancer nanoimmunotherapy.