Persistent luminescence imaging is accompanied by continuous illumination after the removal of excitation light, which can successfully prevent the generation of autofluorescence. In this study, a mesoporous silica template method is used to prepare uniform and monodisperse porous nanophosphors that can generate X‐ray‐excited persistent luminescence (XEPL). By loading photosensitizers, XEPL effectively excites the photosensitizers to produce reactive oxygen species for killing cancer cells. Imaging of orthotopic hepatic tumors in vivo shows that nanophosphors accumulate in the liver tumors through a passive targeting mechanism, as confirmed by the co‐imaging of bioluminescence and X‐ray‐excited luminescence. Under image‐guidance, X‐ray‐induced photodynamic therapy effectively inhibits the growth of orthotopic hepatic tumors with negligible side effects. Overall, X‐ray‐induced persistent luminescence promotes ultrasensitive imaging and effective inhibition of orthotopic hepatic tumors.
Light-mediated therapy has many unique merits but monotherapy strategies rarely completely inhibit tumor growth because resistance often develops. Combination therapy is a promising strategy in oncology and has demonstrated superior safety and efficacy over monotherapy. Here, we conjugated a scintillator complex and gold nanorod nanosensitizer for dual-modal image-guided photothermal and X-ray-induced photodynamic therapy (PDT). Lanthanide complexes were successfully conjugated and offer excellent X-ray-excited optical luminescence for PDT effects. The strong near-infrared (NIR) light and X-ray absorption abilities of gold nanorods make the nanosensitizer function as both a photothermal agent for photothermal therapy and a radiosensitizer for enhanced radiotherapy. The studies in vitro and in vivo demonstrated that the nanosensitizer offers good dual-modal imaging capability and significantly suppresses tumor progression under NIR light and X-ray irradiation. This work shows the great potential of conjugating scintillator lanthanide complexes and gold nanosensitizers for multimodal image-guided therapy of deep-seated tumors.
Paramagnetic complexes containing gadolinium ions have been widely used for magnetic resonance imaging (MRI) in clinic. However, these paramagnetic complexes pose some safety concerns. There is still a demand for the development of stable MRI contrast agents that exhibit higher sensitivity and superior functionality to existing contrast agents. Here, we develop carbonized paramagnetic complexes of manganese (II) (Mn@CCs) to encapsulate Mn2+ in sealed carbonized shells with superhigh r1 relaxivity. Compared to the most common clinical contrast agent Magnevist, investigations in vivo demonstrate that the Mn@CCs cross the intact blood-brain barrier of normal health mice with minor metal deposition; preferentially target the glioma tissues distribute homogeneously with high penetration in an intracranial mouse model; delineate clear tumor margins in MRIs of ultrasmall single-nodule brain tumors, and multi-nodular liver tumors. The sensitivity, accuracy and low toxicity offer by Mn@CCs provides new opportunities for early molecular diagnostics and imaging-guided biomedical applications.
X-ray excited persistent luminescence (XEPL) imaging has attracted increasing attention in biomedical imaging due to elimination of autofluorescence, high signal-to-noise ratio and repeatable activation with high penetration. However, optical imaging still suffers from limited for high spatial resolution. Methods: Herein, we report Mn 3+ -rich manganese oxide (MnO x )-coated chromium-doped zinc gallogermanate (ZGGO) nanoparticles (Mn-ZGGOs). Enhanced XEPL and magnetic resonance (MR) imaging were investigated by the decomposition of MnO x shell in the environment of tumors. We also evaluated the tumor cell-killing mechanism by detection of reactive oxygen (ROS), lipid peroxidation and mitochondrial membrane potential changes in vitro . Furthermore, the in vivo biodistribution, imaging and therapy were studied by U87MG tumor-bearing mice. Results: In the tumor region, the MnO x shell is quickly decomposed to produce Mn 3+ and oxygen (O 2 ) to directly generate singlet oxygen ( 1 O 2 ). The resulting Mn 2+ transforms endogenous H 2 O 2 into highly toxic hydroxyl radical (·OH) via a Fenton-like reaction. The Mn 2+ ions and ZGGOs also exhibit excellent T 1 -weighted magnetic resonance (MR) imaging and ultrasensitive XEPL imaging in tumors. Conclusion: Both the responsive dual-mode imaging and simultaneous self-supplied O 2 for the production of 1 O 2 and oxygen-independent ·OH in tumors allow for more accurate diagnosis of deep tumors and more efficient inhibition of tumor growth without external activation energy.
The catalytic activities of currently developed peroxidase-mimic nanozymes are generally limited. Therefore, further efforts are still needed to improve the catalytic performance of peroxidase nanozymes. Herein, we synthesized Fe-coordinated carbon nanozyme dots (Fe-CDs) that can serve as both efficient peroxidase nanozymes and T 2 -magnetic resonance imaging (MRI) contrast agents. The intrinsic peroxidase-like activity of the Fe-CDs was explored by catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) with hydrogen peroxide (H 2 O 2 ). The product showed better performance over natural horseradish peroxidase (HRP) and other mimetic peroxidases. Quantification of glucose and ascorbic acid detection showed that this nanozyme could be used to detect a minimum limit as low as 5 μM glucose. Moreover, the colorimetric detection technique was used to detect serum glucose in mice, and the detection result was comparable with autobiochemistry analyzer results using a glucose assay kit. Furthermore, the Fe-CDs showed good magnetism properties and provided promising MR imaging of tumors with excellent biocompatibility.
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