Mingyuan Gao

The diagnosis of traumatic brain injury (TBI) remains heavily constrained by the limitations of conventional imaging techniques in visualizing the pathological events that determine the disease progression and outcome. To address this clinical challenge, we report a manganese-doped near-infrared quantum dot (QD) to intrinsically integrate the highly sensitive optical imaging with clinical compatible magnetic resonance imaging (MRI). Taking the advantages of optical imaging powered by whole-brain clearing and cellular resolution three-dimensional (3D) panoptic imaging, in combination with the systematic in vitro cell studies on different types of cells involved in TBI, we disclosed the interpretable pathology reflected by TBI imaging through the highly sensitive fluorescence of magnetic QDs, i.e., after systemic administration, the nanoprobes were extravasated through the compromised blood-brain barrier and then selectively phagocytosed by activated microglia, which subsequently migrated into the regions rich in dead neurons and neuronal debris. This microglia-mediated tropism decodes the signal origin of MRI enhanced by the nanometer-sized contrast agent, thereby transforming the MRI from an anatomical tool into a pathological reporter. A biocompatible Fe ₃ O ₄ nanoparticle of similar size was also compared with the magnetic QD mentioned above for validating the translational merits of nanoparticles in MRI diagnosis of TBI.

The therapeutic efficacy of nanomedicines in solid tumors is often limited by rapid systemic clearance, dense extracellular matrix (ECM) barriers, poor tumor cell selectivity, and an immunosuppressive tumor microenvironment. Herein, we report an active lysosome-encapsulated hollow mesoporous Prussian blue nanoparticle platform that sequentially overcomes these challenges through prolonged circulation, ECM remodeling, tumor-targeted delivery, and immune modulation of the tumor microenvironment in a subcutaneous 4T1 tumor model. The lysosomal membrane enhances biocompatibility and circulation time, facilitating preferential tumor accumulation. Upon arrival, retained lysosomal hydrolases, including cathepsins B, K, L, and S, degrade ECM components, enabling deep nanoparticle penetration and immune cell infiltration. In the tumor parenchyma, lysosomal membrane encapsulation enhances cellular uptake, leading to iron overload and lipid peroxidation-driven ferroptosis, further amplified by nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Proteomic profiling revealed increased oxidative stress and local remodeling of the tumor immune microenvironment, corroborated by dendritic cell maturation, CD8+ T cell infiltration, and macrophage polarization. These effects collectively remodeled the immunosuppressive tumor niche. Compared with conventional biological membrane coatings such as red blood cell-derived vesicles, this lysosome-based system exhibits enhanced tumor accumulation, enzymatic functionality, and immunotherapeutic synergy. These findings highlight lysosome-encapsulated nanomedicine as a potential platform for ECM remodeling-facilitated immunotherapy with broad potential across therapeutic modalities.

Boron neutron capture therapy (BNCT) has received significant attention due to its effectiveness in treating tumors. Preclinical and clinical studies have sought materials with a high boron content. Meanwhile, imaging-guided BNCT can not only enable the determination of the optimal neutron irradiation time and the required dose but also hold substantial significance for evaluating the therapeutic effects. Herein, iron borate (Fe₂B₂O₅) nanobeams were synthesized via the thermal decomposition method. First, iron borate nanobeams are rich in boron, providing sufficient boron for BNCT. Second, the magnetic properties of the nanobeams enable enhancement of magnetic resonance imaging (MRI) contrast, facilitating the monitoring of the agent's distribution. The size and morphology of the nanobeams can be tuned by varying the synthesis temperature, time, and precursor concentration. To enhance the colloidal stability and biocompatibility, the iron borate nanobeams were coated with a layer of silica (IBNBs@SiO₂). The in vitro and in vivo experiments demonstrate that IBNBs@SiO₂ functions as a T1 contrast agent. Furthermore, cells and mice treated with IBNBs@SiO₂ followed by thermal neutron irradiation demonstrated the effective suppression of melanoma growth. Therefore, IBNBs have potential for MRI-guided BNCT.

Designing colloidal assemblies with molecule-like architectures comprising more than two electronically coupled quantum dots has often required technologically complex, expensive, and top-down nanofabrication. Here we demonstrate a one-pot chemical synthesis of dimeric, trimeric, and tetrameric assemblies of coupled molecule-like quantum dots (CMQDs), using ZnSe@ZnS quantum dots as model. We show that the “valence” of these “artificial atoms” can be readily tuned by the amount of a suitable ligand in the reaction mixture, and that high-temperature fusion yields highly ordered oriented attachment and strong electron coupling between bound QDs. The shapes of the fused assemblies echo the canonical sp-, sp²-, and sp³-hybridization motifs and can be interpreted as appropriately shaped confining potential wells for electrons and holes. This work establishes an experimentally accessible entry point to related “artificial molecules” with controllable chemical composition, geometry, and electronic structure. The enhanced or emergent properties of such nanomaterials are anticipated to advance applications in optoelectronics, sensing, and quantum photonic technologies.

The hepatic accumulation of nanoparticles significantly impedes their diagnostic and therapeutic efficacy in biomedical applications. However, the precise role of specific physicochemical properties in determining nanoliver interaction remains poorly understood. This study utilizes ^99mTc-labeled iron oxide nanoparticles to elucidate the effect of size (3.6 and 12.0 nm) and PEG chain length (1K, 2K, and 5K) on their hepatic interactions. In vivo SPECT/CT imaging reveals that small particles initially clear through the kidneys, while large particles predominantly accumulate in the liver and spleen, ultimately showing significant liver uptake. Longer PEG chains generally extend circulation time and slow hepatic uptake, with particles coated with 2K PEG exhibiting the lowest hepatic accumulation, suggesting an optimal balance between circulation time and hepatic sequestration. Complementary in vitro studies with primary liver cells─namely hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), and hepatic stellate cells (HSCs)─reveal complex uptake behaviors significantly influenced by particle size and PEG chain length. Contrary to conventional wisdom, the study identifies an uptake trend of HCs ∼ HSCs > LSECs > KCs, challenging the prevailing notion of KCs as the primary mediators of nanoparticle clearance. Bridging in vitro and in vivo observations, the hepatic accumulation of small particles closely correlates with uptake patterns in primary HCs, while the accumulation of large particles is linked to interactions with LSECs and KCs. These results highlight the importance of cellular microenvironments in nanoliver interactions, offering design guidance for optimizing nanomedicines to achieve enhanced specificity and reduced off-target effects.

Radiotherapy is a fundamental treatment for prostate cancer; however, its therapeutic efficacy is frequently limited by radioresistance mediated through DNA repair mechanisms and other biological factors. Although gene therapy holds promise for overcoming such resistance, identifying effective radiosensitization targets and developing efficient gene delivery systems remain practically challenging. In this study, transcriptomic analysis of radiotherapy‐treated prostate cancer cells revealed a marked upregulation of DNA polymerase delta subunit 4 (POLD4), a target that has not been systematically studied. To evaluate the potential of POLD4 for overcoming radioresistance, CRISPR‐Cas9‐based plasmids along with ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) were encapsulated within cationic liposomes for achieving an MRI‐trackable gene delivery platform (plasmid and iron oxide co‐loaded liposomes, termed PIO@Lipo). Comprehensive in vitro and in vivo studies demonstrated that PIO@Lipo enabled efficient POLD4 knockdown. Furthermore, PIO@Lipo synergized with radiotherapy to induce extensive DNA damage, promote tumor cell apoptosis, and remodel the immunosuppressive microenvironment. Notably, PIO@Lipo displayed superior MRI contrast enhancement capability and passive tumor targeting ability. In conclusion, this study has identified POLD4 as a potent target for radiosensitization, capable of disrupting DNA damage‐repair homeostasis through MRI‐monitored gene editing, thereby offering a promising strategy to enhance the efficacy of radiotherapy in prostate cancer.

Due to the prolonged MRI encoding process, respiratory motion can cause undesired artifacts and image blurring, degrading image quality and limiting clinical applications in abdominal and pulmonary imaging. In this work, we develop a two-stage respiratory motion-resolved radial MR image reconstruction pipeline using an interpretable deep unrolled network (MoraNet), enabling high-quality imaging under free-breathing conditions. Firstly, low-resolution images are reconstructed from the central region of successive golden-angle radial k-space to extract respiratory motion signals. The binned k-space data based on the respiratory signal are then used to reconstruct the motion-resolved high-resolution image for each motion state. The MoraNet applies nonuniform fast Fourier transform (NUFFT) to operate radial encoding and convolutional neural network (CNN) modules to conduct image regularizations. The MoraNet was trained on retrospectively acquired lung MRI images for both fully sampled and undersampled acquisitions. The performance of the proposed method was evaluated on digital CT/MRI breathing XCAT (CoMBAT) phantom data, QUASAR motion phantom data acquired from a 1.0T MRI scanner and volunteer chest data acquired from a 1.5T MRI scanner. The MoraNet pipeline was compared with motion-averaged reconstruction and a conventional compressed sensing (CS)-based method in terms of SSIM, RMSE and computation time. Simulation and experimental results demonstrated that the proposed network could provide accurate respiratory signal estimation and enable effective motion correction. Compared with the CS method, the MoraNet preserved better structural details with lower RMSE and higher SSIM values at acceleration factor of 4, and meanwhile took ten-fold faster inference time.

Endoscopic submucosal dissection (ESD) enables en bloc resection of early gastrointestinal neoplasms but remains constrained by two critical limitations: rapid dissipation of submucosal injectates during surgery and insufficient wound management postresection. To overcome this clinical bottleneck, we develop a multifunctional, clinically translatable injectable hydrogel engineered to unify intraoperative mucosal elevation and postoperative tissue repair. This hydrogel system is synthesized via dynamic cross-linking between oxidized sodium alginate and carboxymethyl chitosan, reinforced with Ca²⁺ coordination to enhance mechanical strength and hemostasis. Phycocyanin, a natural antioxidant protein, is incorporated to provide intraoperative visual contrast and bioactive immunomodulatory properties. The formulation exhibits tunable gelation kinetics, excellent injectability, and self-healing capability compatible with endoscopic delivery. Comprehensive in vitro studies confirm the hydrogel's biocompatibility, antioxidant and anti-inflammatory activity, macrophage M2 polarization, hemostatic performance, and structural self-repair. In ex vivo porcine stomach models, the hydrogel achieves sustained mucosal elevation, significantly outperforming hyaluronic acid-based controls. In large-animal ESD models, it promotes organized collagen deposition, angiogenesis, re-epithelialization, and suppressed fibrotic α-SMA expression, collectively accelerating mucosal regeneration with reduced inflammation. This dual-function platform bridges surgical precision with postresection regeneration, offering a next-generation therapeutic material for minimally invasive gastrointestinal oncology.

Radiolabeled nanoparticles hold great promise in precision medicine due to its versatile applications in disease imaging and therapy. However, its clinical translation is often hindered by excessive accumulation in reticuloendothelial system organs, particularly the liver, which can lead to radiation‐induced toxicity. Herein, an in vivo selective radiolabeling strategy is reported that exploits the distinct subcellular fates of nanoparticles in tumors versus liver. A biorthogonal nanosystem composed of trans‐cyclooctene (TCO)‐functionalized iron oxide nanoparticles (Fe ₃ O ₄ @TCO) and a radiolabeled tetrazine probe ( ¹⁷⁷ Lu‐DOTA‐Tz) is constructed to validate this concept. Owing to the hydrophilic nature, ¹⁷⁷ Lu‐DOTA‐Tz cannot penetrate cell membranes, resulting in spatially restricted bioorthogonal labeling in the extracellular space. At tumor sites, Fe ₃ O ₄ @TCO nanoparticles accumulate via the enhanced permeability and retention effect and remain accessible for efficient binding with ¹⁷⁷ Lu‐DOTA‐Tz. In contrast, in the liver, nanoparticles are predominantly internalized by liver cells, and its intracellular localization prevents interaction with the probe, thereby minimizing hepatic radiation retention. By harnessing these subcellular distribution differences, the approach achieves selective in vivo radiolabeling and significantly improves the tumor‐to‐liver radiation ratio. This study provides a biologically informed strategy for designing radiolabeled nanoplatforms with enhanced safety profiles for theranostic applications.

The development of sustainable and non-invasive method for delivering drugs to the brain is crucial for the effective treatment of Parkinson’s disease (PD). In this study, nanoparticles were formulated by using poly (ethylene glycol)-block-poly (propylene glycol)-block-poly (ethylene glycol) (PEG-b-PPG-b-PEG) to facilitate an efficient intranasal delivery of rotigotine directly into the brain. It was found that the intranasal route enabled more effective accumulation of rotigotine in the brain than conventional intravenous administration, demonstrating its feasibility as an innovative delivery approach for PD treatment. Furthermore, the behavioral test, brain histology and immunochemistry analyses demonstrated a significant improvement in the symptoms of PD-like neurodegeneration in mice treated with intranasally delivered rotigotine-loaded nanoparticles. These outcomes affirm an outstanding therapeutic efficacy of the nano-formulation for intranasal delivery, highlighting its potential for the effective treatment of neurodegenerative disorders, particularly PD.