Target Design of Multinary Metal-Organic Frameworks for Near-Infrared Imaging and Chemodynamic Therapy.

Imaging-guided chemodynamic therapy is widely considered a promising modality for personalized and precision cancer treatment. Combining both imaging and chemodynamic functions in one system conventionally relies on the hybrid materials approach. However, the heterogeneous, ill-defined, and dissociative/disintegrative nature of the composites tends to complicate their action proceedings in biological environments and thus makes the treatment imprecise and ineffective. Herein, a strategy to employ two kinds of inorganic units with different functions─reactive oxygen species generation and characteristic emission─has achieved two single-crystalline metal-organic frameworks (MOFs), demonstrating the competency of reticular chemistry in creating multifunctional materials with atomic precision. The multinary MOFs could not only catalyze the transformation from H2O2 to hydroxyl radicals by utilizing the redox-active Cu-based units but also emit characteristic tissue-penetrating near-infrared luminescence brought by the Yb4 clusters in the scaffolds. Dual functions of MOF nanoparticles are further evidenced by pronounced cell imaging signals, elevated intracellular reactive oxygen species levels, significant cell apoptosis, and reduced cell viabilities when they are taken up by the HeLa cells. In vivo NIR imaging is demonstrated after the MOF nanoparticles are further functionalized. The independent yet interconnected modules in the intact MOFs could operate concurrently at the same cellular site, achieving a high spatiotemporal consistency. Overall, our work suggests a new method to effectively accommodate both imaging and therapy functions in one well-defined material for precise treatment.

Ultrasound image segmentation using Gamma combined with Bayesian model for focused-ultrasound-surgery lesion recognition.

This study aims to investigate the feasibility of combined segmentation for the separation of lesions from non-ablated regions, which allows surgeons to easily distinguish, measure, and evaluate the lesion area, thereby improving the quality of high-intensity focused-ultrasound (HIFU) surgery used for the non-invasive tumor treatment. Given that the flexible shape of the Gamma mixture model (GΓMM) fits the complex statistical distribution of samples, a method combining the GΓMM and Bayes framework is constructed for the classification of samples to obtain the segmentation result. An appropriate normalization range and parameters can be used to rapidly obtain a good performance of GΓMM segmentation. The performance values of the proposed method under four metrics (Dice score: 85%, Jaccard coefficient: 75%, recall: 86%, and accuracy: 96%) are better than those of conventional approaches including Otsu and Region growing. Furthermore, the statistical result of sample intensity indicates that the finding of the GΓMM is similar to that obtained by the manual method. These results indicate the stability and reliability of the GΓMM combined with the Bayes framework for the segmentation of HIFU lesions in ultrasound images. The experimental results show the possibility of combining the GΓMM with the Bayes framework to segment lesion areas and evaluate the effect of therapeutic ultrasound.

Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells.

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnOx -loaded polydopamine (MnOx /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnOx /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnOx /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnOx /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.

Tensile-Strained Palladium Nanosheets for Synthetic Catalytic Therapy and Phototherapy.

Palladium nanosheets (Pd NSs) are well-investigated photothermal therapy agents, but their catalytic potential for tumor therapy has been underexplored owing to the inactive dominant (111) facets. Herein, lattice tensile strain is introduced by surface reconstruction to activate the inert surface, endowing the strained Pd NSs (SPd NSs) with photodynamic, catalase-like, and peroxidase-like properties. Tensile strain promoting the photodynamic and enzyme-like activities is revealed by density functional theory calculations. Compared with Pd NSs, SPd NSs exhibit lower photothermal effect, but approximately five times higher tumor inhibition rate. This work calls for further study to activate nanomaterials by strain engineering and surface reconstruction for catalytic therapy of tumors.

A Photoresponsive Nanozyme for Synergistic Catalytic Therapy and Dual Phototherapy.

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (•OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.