Eye infection is one of the most important causes of blindness. Due to the particularity of ocular structure, the enhancement of bacteria resistance, and the significant side effects of long-term medication, it is difficult to treat ocular antimicrobial diseases. The efficacy of medications currently employed is progressively becoming more restricted. The research and development of novel antimicrobial drugs is imperative and imminent in order to overcome the bottleneck problem. Metal nanoparticles have been developed rapidly in the field of biomedicine because of their brilliant antibacterial activity, long-lasting effect, and great bioavailability. Efficacy and biosafety proven in in vitro and in vivo experiments demonstrate the promising prospect of metal nanoparticles for ocular antimicrobial therapy. Based on the development status of antibacterial metal nanoparticles in ophthalmology, we summarized the antibacterial mechanism of metal nanoparticles and the application of nano-antibacterial drugs in this field, emphasizing their advantages over conventional drugs, thus guiding clinical ophthalmic antibacterial therapy.

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination.

Cerebral ischemia-reperfusion injury (CIRI) is a major challenge to neuronal survival in acute ischemic stroke (AIS). However, effective neuroprotective agents remain to be developed for the treatment of CIRI. In this work, we have developed an Anti-TRAIL protein-modified and indocyanine green (ICG)-responsive nanoagent (Anti-TRAIL-ICG) to target ischemic areas and then reduce CIRI and rescue the ischemic penumbra. In vitro and in vivo experiments have demonstrated that the carrier-free nanoagent can enhance drug transport across the blood-brain barrier (BBB) in stroke mice, exhibiting high targeting ability and good biocompatibility. Anti-TRAIL-ICG nanoagent played a better neuroprotective role by reducing apoptosis and ferroptosis, and significantly improved ischemia-reperfusion injury. Moreover, the multimodal imaging platform enables the dynamic in vivo examination of multiple morphofunctional information, so that the dynamic molecular events of nanoagent can be detected continuously and in real time for early treatment in transient middle cerebral artery occlusion (tMCAO) models. Furthermore, it has been found that Anti-TRAIL-ICG has great potential in the functional reconstruction of neurovascular networks through optical coherence tomography angiography (OCTA). Taken together, our work effectively alleviates CIRI after stoke by blocking multiple cell death pathways, which offers an innovative strategy for harnessing the apoptosis and ferroptosis against CIRI.

Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV.

Pancreatic cancer is a deadly disease with a five-year overall survival rate of around 11%. Chemotherapy is a cornerstone in the treatment of this malignancy, but the intratumoral delivery of chemotherapy drugs is impaired by the highly fibrotic tumor-associated stroma. Irreversible electroporation (IRE) is an ablative technique for treating locally advanced pancreatic cancer. During a typical IRE procedure, high-intensity electric pulses are released to kill tumor cells through the irreversible disruption of the cytoplasm membranes. IRE also induces rapid tumor infiltration by neutrophils and offers an opportunity for neutrophil-mediated drug delivery. We herein showed that the IRE-induced neutrophil trafficking was facilitated by the upregulation of neutrophil chemotaxis and migration as well as the release of several chemoattractants. Doxorubicin-loaded bovine serum albumin nanoparticles were prepared and loaded into neutrophils at a ratio of 9.9 ± 1.2 to 11.7 ± 2.0 pg of doxorubicin per cell. The resultant formulation (NP@NEs) efficiently accumulated in the IRE-treated KPC-A377 murine pancreatic tumors with an uptake value of 10.7 ± 1.5 (percent of injected dose per gram of tissue, abbreviated as %ID/g) at 48 h after intravenous injection. In both Panc02 and KPC-A377 murine pancreatic tumor models, the combination of IRE + NP@NEs inhibited tumor growth more effectively than either monotherapy. The tumors treated with the combination also exhibited the lowest frequency of Ki67+ proliferating cells and the highest abundance of terminal deoxynucleotidyl transferase dUTP nick end labeling+ (TUNEL+) apoptotic cells among the experiment groups. Minimal treatment-associated toxicity was observed. Our findings suggest that neutrophil-mediated delivery of chemotherapy drugs is a useful tool to enhance the response of pancreatic cancer to IRE.

Laser speckle contrast imaging (LSCI) is a noninvasive, label-free technique that allows real-time investigation of the microcirculation situation of biological tissue. High-quality microvascular segmentation is critical for analyzing and evaluating vascular morphology and blood flow dynamics. However, achieving high-quality vessel segmentation has always been a challenge due to the cost and complexity of label data acquisition and the irregular vascular morphology. In addition, supervised learning methods heavily rely on high-quality labels for accurate segmentation results, which often necessitate extensive labeling efforts. Here, we propose a novel approach LSWDP for high-performance real-time vessel segmentation that utilizes low-quality pseudo-labels for nonmatched training without relying on a substantial number of intricate labels and image pairing. Furthermore, we demonstrate that our method is more robust and effective in mitigating performance degradation than traditional segmentation approaches on diverse style data sets, even when confronted with unfamiliar data. Importantly, the dice similarity coefficient exceeded 85% in a rat experiment. Our study has the potential to efficiently segment and evaluate blood vessels in both normal and disease situations. This would greatly benefit future research in life and medicine.

BACKGROUND/AIM:Probing brain tumor microvasculature holds significant importance in both basic cancer research and medical practice for tracking tumor development and assessing treatment outcomes. However, few imaging methods commonly used in clinics can noninvasively monitor the brain microvascular network at high precision and without exogenous contrast agents in vivo. The present study aimed to investigate the characteristics of microvasculature during brain tumor development in an orthotopic glioma mouse model.MATERIALS AND METHODS:An orthotopic glioma mouse model was established by surgical orthotopic implantation of U87-MG-luc cells into the mouse brain. Then, optical coherence tomography angiography (OCTA) was utilized to characterize the microvasculature progression within 14 days.RESULTS:The orthotopic glioma mouse model evaluated by bioluminescence imaging and MRI was successfully generated. As the tumor grew, the microvessels within the tumor area slowly decreased, progressing from the center to the periphery for 14 days.CONCLUSION:This study highlights the potential of OCTA as a useful tool to noninvasively visualize the brain microvascular network at high precision and without any exogenous contrast agents in vivo.

Radioactive microspheres have shown excellent therapeutic effects in the treatment of advanced hepatocellular carcinoma (HCC) due to indiscriminate embolization and killing of tumor cells. However, limitations such as unstable loading, in vivo reflux, and untrackable radioactive microspheres restrict their clinical applicability. Herein, a novel injectable lutetium‐177‐labeled 3D hollow porous radio‐granular hydrogels with a double‐cross‐linked network ( 177 Lu‐3D‐HPGH) are synthesized via microfluidics combined with ultraviolet photo‐cross‐linking technology is reported. The radiolabeling efficiency of 177 Lu‐3D‐HPGH can reach 97.85%. The 3D hollow porous radio‐granular hydrogels exhibited uniform, controllable size, radio‐theranostics, and excellent underwater adhesion properties, avoiding unwanted radiation damage to non‐target organs. Particularly, the extended X‐ray absorption fine structure combined with the density functional theory calculation revealed the mechanism of 3D‐HPGH loading with 177 Lu through Lu‐N/O coordination. Furthermore, rabbit orthotopic kidney and liver tumor models are used to verify the excellent embolization performance, radionuclide loading stability, anti‐reflux characteristics, anti‐tumor effect, and biosafety of 177 Lu‐3D‐HPGH. Briefly, this facile, green, and safe synthesis strategy provides a superior choice for intravascular brachytherapy of HCC and has great application value and transformative potential in clinical diagnosis and treatment.

Photodynamic therapy (PDT) is an alternative cancer treatment technique with a noninvasive nature, high selectivity, and minimal adverse effects. The indispensable light source used in PDT is a critical factor in determining the energy conversion of photosensitizers (PSs). Traditional light sources are primarily concentrated in the visible light region, severely limiting their penetration depth and making them prone to scattering and absorption when applied to biological tissues. For that reason, its efficacy in treating deep-seated lesions is often inadequate. Self-exciting PDT, also known as auto-PDT (APDT), is an attractive option for circumventing the limited penetration depth of traditional PDT and has acquired significant attention. APDT employs depth-independent internal light sources to excite PSs through resonance or radiative energy transfer. APDT has considerable potential for treating deep-tissue malignancies. To facilitate many researchers' comprehension of the latest research progress in this field and inspire the emergence of more novel research results. This review introduces internal light generation mechanisms and characteristics and provides an overview of current research progress based on the recently reported APDT nanoplatforms. The current challenges and possible solutions of APDT nanoplatforms are also presented and provide insights for future research in the final section of this article.

Surgical resection (SR) is the major method for treating invasive or recurrent noninvasive bladder cancer (BC). However, SR still causes additional risks of urinary tract infection, bleeding and some complications that may be life-threatening. Therefore, it is of urgent medical need for new diagnosis and therapy scheme for BC. Herein, we proposed a strategy that combines dual-modality three-dimensional (3D) NIR-II photoacoustic (PA) and optical coherence tomography angiography (OCTA) molecular imaging to guide visually interventional photothermal therapy (PTT) for BC. Additionally, we developed an excellent NIR-II hyaluronic acid-IR-1048 with liposome- coated (HAPO-1048) photothermal agent for PTT of CD44 overexpressing orthotopic BC, which showed strong NIR-II optical absorption, preferable tumor targeting, excellent biocompatibility and high PTT efficacy. Combined with the NIR-II PA/PTT response of the HAPO-1048, we can achieve high sensitivity and specificity (about 2 mm diameter) dynamic monitoring and investigate the precision therapy of PTT in deep orthotopic BC (4.38 mm). Simultaneously, we can map the dynamic changes of 3D PA signals and HAPO-1048 nanoparticles (HAPO-1048 NPs) enrichment, which is closely related to the PTT efficacy. Significantly, the whole changes of complex microvascular morphometrics and angiogenesis of BC were well surveilled and assessed in vivo using OCTA. Lastly, minimally invasive interventional PTT strategy was successfully implemented to achieve a controllable and precise therapy for orthotopic BC based on laparoscopy and US guidance. In conclusion, we present a multimodal NIR-II optical imaging synergy laparoscopy interventional oncologic scheme, which should expand the current PTT technology, leading to a significant ongoing in treatment of primary tumors of urinary system