Luminescent properties of Er^(3+)-and Yb^(3+)-co-doped CaF_(2)upconversion nanoparticles(UCNPs)were investigated in single particle and densely-packed states with a custom-built microscope.The single UCNPs exhibit lin...Luminescent properties of Er^(3+)-and Yb^(3+)-co-doped CaF_(2)upconversion nanoparticles(UCNPs)were investigated in single particle and densely-packed states with a custom-built microscope.The single UCNPs exhibit linear dependency of luminescent intensity on excitation power while the densely-packed UCNPs exhibit a 2-order power law-dependency indicating a two-photon absorption process.Time-domain luminescence intensity measurements were performed and the curves were fitted to excitationnemission rate functions based on a simplified three-state model.The results indicate that the intermediates in single particles are much less and saturated in a short time,and there are strong couplings of the ground states and intermediate states between neighboring UCNPs in densely packed UCNPs.展开更多
Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery sy...Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells(DCs)for initiating high T cell immunity.Herein,antigen-loaded manganese oxide(Mn_(3)O_(4))triangular-shaped ultrasmall nanoparti-cles were prepared to stimulate DC-based immunotherapy under the guidance of T_(1)magnetic resonance imaging.The FDA-approved triblock copolymer Pluronic^(■)F-68 wasused not onlyto transferthe phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles.Ovalbumin(OVA),a model antigen,was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn_(3)O_(4)@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity.The Mn_(3)O_(4)@PF68-OVA nanovaccine(NV)induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells(BMDCs)by conventional methods supports the proliferation of intestine organoids,which are an innovative three-dimensional cytotoxicity evaluation system,thereby indicating their potential safety for in vivo cancer therapies.The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs.In ad-dition,Mn_(3)O_(4)@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages,which suggests improved immunity.Excitingly,vaccination with Mn_(3)O_(4)@PF68-OVA offer complete pro-tection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor.In addition,the designed nanovaccine demonstrated high T_(1)-MR imaging in the tumor,fur-ther justifying enhanced tumor accumulation and capability to real-time monitor the treatment proce-dure.This study presents a promising nanosystem to design an effective nanovaccine for T_(1)-MR imaging-guided tumor immunotherapy.展开更多
基金The work was supported by the National Key Research and Development Program of China(YFC20170110100)the National Natural Science Foundation of China(NSFC)(Grant Nos.61475185 and 11504409)Natural Science Foundation of Tianjin City(TJNSF)(Grant No.16JCYBJC43800).Xiaohu Chen and Zhengyu Gui contributed equality to this work.
文摘Luminescent properties of Er^(3+)-and Yb^(3+)-co-doped CaF_(2)upconversion nanoparticles(UCNPs)were investigated in single particle and densely-packed states with a custom-built microscope.The single UCNPs exhibit linear dependency of luminescent intensity on excitation power while the densely-packed UCNPs exhibit a 2-order power law-dependency indicating a two-photon absorption process.Time-domain luminescence intensity measurements were performed and the curves were fitted to excitationnemission rate functions based on a simplified three-state model.The results indicate that the intermediates in single particles are much less and saturated in a short time,and there are strong couplings of the ground states and intermediate states between neighboring UCNPs in densely packed UCNPs.
基金financially supported by the National Natural Science Foundation of China(No.51672250 and 51902289)the Zhejiang International Science and Technology Cooperation Project(Nos.2021C01180 and 2019C04020)the Research Foundation of ZSTU(No.18012134-Y).
文摘Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells(DCs)for initiating high T cell immunity.Herein,antigen-loaded manganese oxide(Mn_(3)O_(4))triangular-shaped ultrasmall nanoparti-cles were prepared to stimulate DC-based immunotherapy under the guidance of T_(1)magnetic resonance imaging.The FDA-approved triblock copolymer Pluronic^(■)F-68 wasused not onlyto transferthe phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles.Ovalbumin(OVA),a model antigen,was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn_(3)O_(4)@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity.The Mn_(3)O_(4)@PF68-OVA nanovaccine(NV)induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells(BMDCs)by conventional methods supports the proliferation of intestine organoids,which are an innovative three-dimensional cytotoxicity evaluation system,thereby indicating their potential safety for in vivo cancer therapies.The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs.In ad-dition,Mn_(3)O_(4)@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages,which suggests improved immunity.Excitingly,vaccination with Mn_(3)O_(4)@PF68-OVA offer complete pro-tection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor.In addition,the designed nanovaccine demonstrated high T_(1)-MR imaging in the tumor,fur-ther justifying enhanced tumor accumulation and capability to real-time monitor the treatment proce-dure.This study presents a promising nanosystem to design an effective nanovaccine for T_(1)-MR imaging-guided tumor immunotherapy.
