Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Preparation and characterization of QDs-loaded PLGA microbubbles as fluorescent-ultrasonic dual-modality imaging agent / 中华超声影像学杂志

Objective To prepare the quantum dots(QDs) (CdTe-MPA)-loaded polymer(lactic-coglycolic acid,PLGA) microbubbles(MBQDs@PLGA) as dual-modality imaging agent for both fluorescent and ultrasonic imaging ability.Methods The MBQDs@PLGA were generated by the double emulsion technique,then filling in C3F8 after freeze-drying.Confocal laser scanning microscope(CLSM) and transmission electron microscope(TEM) were used to confirm the load of quantum dots in the MBs.Fluorospectro photometer spectra of the MBQDs@PLGA were analyzed to demonstrate the fluorescent imaging ability and determine the encapsulation efficiency by using the regression equation.Imaging experiments was applied to validate the fluorescent and ultrasonic imaging ability of the MBQDs@PLGA both by imaging of the model in vitro and by imaging of ovarian tumor blood vessels of tumor-bearing nude mouse in vivo.Results At excitation 272 nm the MBQDs@PLGA peak of the emission spectrum was 549 nm,and the encapsulation efficiency was 54％.The average diameter of MBQDs@PLGA was (1.7 ±0.2)μm,CLSM and TEM results confirmed the QDs-loaded in MBQDs-PLGA.The imaging results of MBQDs@PLGA showed a dual-modality imaging ability both fluorescent and ultrasonic imaging.Conclusions MBQDs@PLGA present fluorescence-ultrasound dual mode imaging performance by the QDs embedding in polymer microbubbles,and explore a new development train of thought of multi-mode imaging agent.