Graphene Oxide Based Theranostic Platform for <i>T</i>₁‑Weighted Magnetic Resonance Imaging and Drug Delivery

Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the quality of MRI-based diagnosis. In this work, we developed a positive <i>T</i>₁ MRI CA based on graphene oxide (GO)–gadolinium (Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO, followed by Gd­(III) complexation, to form a <i>T</i>₁ MRI CA (GO–DTPA–Gd). We have demonstrated that the GO–DTPA–Gd system significantly improves MRI <i>T</i>₁ relaxivity and leads to a better cellular MRI contrast effect than Magnevist, a commercially used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface of GO sheets via physisorption. Thus-prepared GO–DTPA–Gd/DOX shows significant cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to build a GO-based theranostic nanoplatform with <i>T</i>₁-weighted MRI, fluorescence imaging, and drug delivery functionalities

Enhanced Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells on Graphene Oxide-Incorporated Electrospun Poly(lactic-<i>co</i>-glycolic acid) Nanofibrous Mats

Currently, combining biomaterial scaffolds with living stem cells for tissue regeneration is a main approach for tissue engineering. Mesenchymal stem cells (MSCs) are promising candidates for musculoskeletal tissue repair through differentiating into specific tissues, such as bone, muscle, and cartilage. Thus, successfully directing the fate of MSCs through factors and inducers would improve regeneration efficiency. Here, we report the fabrication of graphene oxide (GO)-doped poly­(lactic-<i>co</i>-glycolic acid) (PLGA) nanofiber scaffolds via electrospinning technique for the enhancement of osteogenic differentiation of MSCs. GO-PLGA nanofibrous mats with three-dimensional porous structure and smooth surface can be readily produced via an electrospinning technique. GO plays two roles in the nanofibrous mats: first, it enhances the hydrophilic performance, and protein- and inducer-adsorption ability of the nanofibers. Second, the incorporated GO accelerates the human MSCs (hMSCs) adhesion and proliferation versus pure PLGA nanofiber and induces the osteogenic differentiation. The incorporating GO scaffold materials may find applications in tissue engineering and other fields

An Immunocompetent Hafnium Oxide-Based STING Nanoagonist for Cancer Radio-immunotherapy

cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core–shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy