ABSTRACT
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.
ABSTRACT
Objective To construct the LyP-1 targeted MR fluorescence dual-modality molecular probe for pancreatic cancer,and to observe its features and MRI charicteristics.Methods The 50 nm MR-fluorescent dual-modality molecular probe with surface modified with cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly Cys) was rationally designed.Whether the molecular probe could specifically recognize the pancreatic cancer cells were validated by the combination of fluorescent imaging and MR T2WI.Results The new MR-fluorescent dual-modality molecular probe anchored with LyP-1 could be used for the fluorescent imaging and MR T2WI of pancreatic cancer in mouse.And the molecular probe was demonstrated to be effective in conjugating with pancreatic cancer cells on fluorescent images and caused obvious MR signal reduction under T2 relaxometry in vitro.In vivo experiment,the molecular probe could be used for fluorescent labeling tumor tissue and detecting orthotopic pancreatic cancer in C57BL/6 mouse as MR contrast agent.Conclusion The LyP1 immobilized MR-fluorescent dual-modality molecular probe can actively target to mouse orthotopic xenograft of pancreatic cancer,which is hopeful to the application in early probing and diagnosis of pancreatic cancer by multimodal imaging.
ABSTRACT
Objective To construct the LyP-1 targeted MR fluorescence dual-modality molecular probe for pancreatic cancer,and to observe its features and MRI charicteristics.Methods The 50 nm MR-fluorescent dual-modality molecular probe with surface modified with cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly Cys) was rationally designed.Whether the molecular probe could specifically recognize the pancreatic cancer cells were validated by the combination of fluorescent imaging and MR T2WI.Results The new MR-fluorescent dual-modality molecular probe anchored with LyP-1 could be used for the fluorescent imaging and MR T2WI of pancreatic cancer in mouse.And the molecular probe was demonstrated to be effective in conjugating with pancreatic cancer cells on fluorescent images and caused obvious MR signal reduction under T2 relaxometry in vitro.In vivo experiment,the molecular probe could be used for fluorescent labeling tumor tissue and detecting orthotopic pancreatic cancer in C57BL/6 mouse as MR contrast agent.Conclusion The LyP1 immobilized MR-fluorescent dual-modality molecular probe can actively target to mouse orthotopic xenograft of pancreatic cancer,which is hopeful to the application in early probing and diagnosis of pancreatic cancer by multimodal imaging.
ABSTRACT
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.
ABSTRACT
Small animal models are extensively utilized in the study of biomedical sciences. Current animal experiments and analysis are largely restricted to in vitro measurements and need to sacrifice animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural evolution of the process under study. Imaging techniques can provide repeatedly in vivo anatomic and molecular information noninvasively. Small animal imaging systems have been developed to assess biological process in experimental animals and increasingly employed in the field of molecular imaging studies. This review outlines the current developments in nuclear medicine imaging instrumentations including fused multi-modality imaging systems for small animal imaging.