“Electron Transport Chain Interference” Strategy of Amplified Mild-Photothermal Therapy and Defect-Engineered Multi-Enzymatic Activities for Synergistic Tumor-Personalized Suppression

Arming activatable mild-photothermal therapy (PTT) with the property of relieving tumor thermotolerance holds great promise for overcoming traditional mild PTT limitations such as thermoresistance, insufficient therapeutic effect, and off-target heating. Herein, a mitochondria-targeting, defect-engineered AFCT nanozyme with enhanced multi-enzymatic activity was elaborately designed as a tumor microenvironment (TME)-activatable phototheranostic agent to achieve remarkable anti-tumor therapy via “electron transport chain (ETC) interference and synergistic adjuvant therapy”. Density functional theory calculations revealed that the synergistic effect among multi-enzyme active centers endows the AFCT nanozymes with excellent catalytic activity. In TME, open sources of H2O2 can be achieved by superoxide dismutase-mimicking AFCT nanozymes. In response to the dual stimuli of H2O2 and mild acidity, the peroxidase-mimicking activity of AFCT nanozymes not only catalyzes the accumulation of H2O2 to generate ·OH but also converts the loaded 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form with strong near-infrared absorption, specifically unlocking its photothermal and photoacoustic imaging properties. Intriguingly, the undesired thermoresistance of tumor cells can be greatly alleviated owing to the reduced expression of heat shock proteins enabled by NADH POD-mimicking AFCT-mediated NADH depletion and consequent restriction of ATP supply. Meanwhile, the accumulated ·OH can facilitate both apoptosis and ferroptosis in tumor cells, resulting in synergistic therapeutic outcomes in combination with TME-activated mild PTT

Quad-Model Imaging-Guided High-Efficiency Phototherapy Based on Upconversion Nanoparticles and ZnFe₂O₄ Integrated Graphene Oxide

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe₂O₄ nanoparticles and upconversion luminescence nanoparticles (UCNPs) on graphene oxide (GO) nanosheets (GO/ZnFe₂O₄/UCNPs, abbreviated as GZUC). To solve the penetration question, here we introduced Tm³⁺-doped UCNPs to convert the high-penetrated near-infrared (NIR) light into UV/vis photons to activate the photodynamic process. In this system, the dual phototherapy from GO and ZnFe₂O₄ has been realized upon NIR laser irradiation. Combined with the photodynamic therapy (PDT) based on Fenton reaction that ZnFe₂O₄ nanoparticles react with excessive H₂O₂ in tumor microenvironment to produce toxic hydroxyl radicals (·OH), an excellent anticancer efficiency has been achieved. Furthermore, 4-fold imaging including upconversion luminescence (UCL), computed tomography (CT), magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) has been obtained due to its intrinsic properties, thereby successfully realizing diagnosis-monitored therapy. Our demonstration provided a feasible strategy to solve the main problems in current light-triggered theranostic

Bismuth Nanoparticles with “Light” Property Served as a Multifunctional Probe for X‑ray Computed Tomography and Fluorescence Imaging

The development of the advanced imaging probe holds the key to the achievement of target imaging and metastasis tracing. The bismuth based nanoprobe has been regarded as the most promising X-ray computed tomography probe due to its largest X-ray attenuation coefficient. Accordingly, the bismuth nanoparticles with controllable size distribution and light weight have been fabricated through a one pot synthesis strategy. The surface modification can be easily conducted with the polyethylene glycol to make the nanoparticles hydrosoluble and biocompatible. More importantly, the Bi nanoparticles can be excited by light to conduct excitation wavelength dependent emission in the visible (Vis) and near-infrared (NIR) region, which makes it possible to utilize it for fluorescence imaging. Under the detection of the multimode CT/fluorescence imaging, the long circulation time of the Bi nanoparticles and its specific accumulation at the liver and intestine can be visually displayed. The facile and large scale preparation method, unique luminescence property, and multimode imaging function endow the Bi nanoparticles with promising applications in clinical diagnosis