Near-Infrared Dye-Loaded Thermosensitive Hydrogels as Novel Fluorescence Tissue Markers.

Accurate intraoperative localization of deep-seated lesions remains a major challenge in minimally invasive procedures such as laparoscopic and robotic surgeries. Current marking strategies-including ink tattooing and metallic clips-are limited by dye diffusion, or poor intraoperative visibility. To address these issues, we developed and evaluated four thermosensitive injectable hydrogel systems incorporating indocyanine green-human serum albumin (ICG-HSA) complexes: (1) hexanoyl glycol chitosan (HGC), (2) Pluronic F-127, (3) PCL-PEG-PCL, and (4) PLA-PEG-PLA.

Zwitterionic alginate derivative as a new delivery platform for enhanced blood circulation.

Purpose: Poly(ethylene glycol) (PEG), a synthetic polymer known for its hydrophilicity and biocompatibility, has long been used in drug delivery systems to prevent non-specific protein adsorption and to extend the blood circulation time of drug carriers and protein drugs. However, PEG has several drawbacks including poor stability, accumulated toxicity, and immunogenicity induced by repeated injections. Recently, zwitterionic polymers, known for their super-hydrophilic and antifouling properties, have been considered excellent alternatives to PEG.

Indocyanine Green-Loaded Quenched Nanoliposomes as Activatable Theranostics for Cancer.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are considered to be one of the most effective methods for treating cancer due to their noninvasive nature, high effectiveness, and fewer side effects compared to standard therapeutic modalities for cancer. However, conventional always-on types of PDT and PTT agents have basic drawbacks in their in vivo applications, which include the unwanted generation of strong fluorescence signals and phototoxicity in normal tissues, including blood vessels, when exposed to light, resulting in poor imaging contrast and unwanted phototoxicity. Here, we propose indocyanine green-loaded quenched nanoliposomes (Q-ICG-NLs) as an activatable nanotheranostics.

Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null-homozygote (N-H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles.

MicBall800-coated metal clip as a novel fluorescent marker for image-guided laparoscopic surgery.

Accurate tumor localization is crucial for the success of minimally invasive surgery, as it minimizes the resection of normal tissues surrounding tumors. Traditional methods for marking gastrointestinal (GI) tumors, such as ink tattooing, intraoperative gastroscopy or colonoscopy, and placement of metal clips, have major drawbacks in their application in laparoscopic surgery. Therefore, the development of safe and easy-to-operate marking methods for accurate and real-time detection of GI tumors during laparoscopic surgery remains an ongoing challenge.

Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced immunotherapy.

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings.

Activatable near-infrared fluorescence probe for real-time imaging of PD-L1 expression in tumors.

In clinical practice, determining programmed death-ligand 1 (PD-L1) expression is crucial for selecting patients and monitoring immune checkpoint blockade therapies. Currently, PD-L1 expression is quantified using immunohistochemistry (IHC). However, IHC-based methods do not capture the heterogeneous and dynamic nature of PD-L1 expression.

Quenched Zwitterionic Cyclic Arg-Gly-Asp-Containing Pentapeptide Probe for Real-Time Brain Tumor Imaging.

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues.

Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies.

Development of polysaccharide-complexed nano-sized rice protein dispersion.

The objective of this study was to improve water solubility of the rice protein (RP) by forming complexes with anionic polysaccharides, such as sodium alginate (SA) and xanthan gum (XG). In addition, utilization of the RP complexes as an emulsifier was evaluated. The prepared RP-SA or RP-XG complexes were analyzed by measuring their particle size, ζ-potential, and water solubility as well as by confocal laser scanning microscopy.

Real-Time Monitoring of Colorectal Cancer Location and Lymph Node Metastasis and Photodynamic Therapy Using Fucoidan-Based Therapeutic Nanogel and Near-Infrared Fluorescence Diagnostic-Therapy System.

We report real-time monitoring of colorectal cancer, lymph node metastasis of colorectal cancer cells, and tumor growth inhibition through photodynamic therapy (PDT) using a near-infrared fluorescence diagnostic-therapy system with a light source for PDT and a fucoidan-based theranostic nanogel (CFN-gel) with good accumulation efficiency in cancer cells. To confirm the effect of the fabricated system and developed CFN-gel, in vitro and in vivo experiments were performed. Chlorin e6 (Ce6) and 5-aminolevulinic acid (5-ALA) were used for comparison.

FOXM1 Inhibition Enhances the Therapeutic Outcome of Lung Cancer Immunotherapy by Modulating PD-L1 Expression and Cell Proliferation.

Programmed death-ligand 1 (PD-L1) is a major target to cancer immunotherapy, and anti-PD-L1 and anti-PD-1 antibody-mediated immunotherapy are being increasingly used. However, immune checkpoint inhibitors (ICIs) are ineffective in treating large tumors and cause various immune-related adverse events in nontarget organs, including life-threatening cardiotoxicity. Therefore, the development of new therapeutic strategies to overcome these limitations is crucial.

Development of Intraoperative Near-Infrared Fluorescence Imaging System Using a Dual-CMOS Single Camera.

We developed a single-camera-based near-infrared (NIR) fluorescence imaging device using indocyanine green (ICG) NIR fluorescence contrast agents for image-induced surgery. In general, a fluorescent imaging system that simultaneously provides color and NIR images uses two cameras, which is disadvantageous because it increases the imaging head of the system. Recently, a single-camera-based NIR optical imaging device with quantum efficiency partially extended to the NIR region was developed to overcome this drawback.

Early On-Treatment Prediction of the Mechanisms of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors.

Background: Prediction of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) remains challenging. Thus, we investigated whether resistant cancer cells that expand shortly after EGFR-TKI treatment would eventually cause the resistant phenotype.

Methods: We generated two -mutant lung cancer cell lines resistant to gefitinib (PC9GR and HCC827GR).

A Quenched Annexin V-Fluorophore for the Real-Time Fluorescence Imaging of Apoptotic Processes In Vitro and In Vivo.

Annexin-based probes have long been used to study apoptotic cell death, which is of key importance to many areas of biological research, drug discovery, and clinical applications. Although apoptosis is a dynamic biological event with cell-to-cell variations, current annexin-based probes are impractical for monitoring apoptosis in real-time. Herein, a quenched annexin V-near-infrared fluorophore conjugate (Q-annexin V) is reported as the first OFF-ON annexin protein-based molecular sensor for real-time near-infrared fluorescence imaging of apoptosis.

Ubiquinone-BODIPY nanoparticles for tumor redox-responsive fluorescence imaging and photodynamic activity.

Successful applications of photodynamic therapy (PDT) in cancer treatment require the development of effective photosensitizers with controllable singlet oxygen generation. Here we report a ubiquinone-BODIPY photosensitizer that self-assembles into nanoparticles (PS-Q-NPs) and undergoes selective activation and deaggregation within the highly reductive intracellular environment of tumor cells. PS-Q-NPs are highly stable in aqueous buffer solution, and exhibit minimal fluorescence and photosensitization due to a rapid non-radiative relaxation process.

Quenched cetuximab conjugate for fast fluorescence imaging of EGFR-positive lung cancers.

Cetuximab-dye conjugates have shown great potential for image-guided surgery of epidermal growth factor receptor (EGFR)-positive cancers in clinical trials. However, their long circulation half-life and prolonged generation of high background signals require the injection of antibody conjugates several days prior to imaging, which limits the clinical applications. Herein, we developed a cetuximab-ATTO655 conjugate (i.

Hydroxychloroquine-loaded hollow mesoporous silica nanoparticles for enhanced autophagy inhibition and radiation therapy.

Radiotherapy (RT) is a major modality for cancer treatment, along with surgery and chemotherapy. Despite its therapeutic effect, the recurrence and metastasis of tumors due to the acquired resistance of cancer cells to RT remain significant clinical problems. Therefore, it is imperative to overcome radioresistance and improve radiosensitivity in cancer patients.

Indocyanine green-loaded injectable alginate hydrogel as a marker for precision cancer surgery.

Background: Accurate identification of tumor sites and boundaries is of paramount importance during minimally invasive surgery. Although laparoscopic resection is being increasingly and widely performed for early gastric and colorectal cancers, the detection of tumors located inside the stomach and intestine is difficult owing to the lack of tactile sensation. Here, we propose the application of an indocyanine green (ICG)-loaded alginate hydrogel system as a fluorescence surgical marker for precise laparoscopic operations.

Fucoidan-Based Theranostic Nanogel for Enhancing Imaging and Photodynamic Therapy of Cancer.

In this study, a fucoidan-based theranostic nanogel (CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve activatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy (PDT) to induce the complete death of cancer cells. A CFN-gel has nanomolar affinity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention effect.

Mini-Platform for Off-On Near-Infrared Fluorescence Imaging Using Peptide-Targeting Ligands.

Here, we propose a zwitterionic near-infrared (NIR) fluorophore-tryptophan (Trp) conjugate with a cleavable linker as a minimal-sized versatile platform (MP) for the preparation of peptide ligand-based off-on type molecular probes. The zwitterionic NIR fluorophore in MP undergoes fluorescence quenching via a photoinduced electron transfer mechanism when in close proximity to tryptophan, and nonspecific binding with serum proteins is minimized by the zwitterionicity of the fluorophore. The linker can be cleaved inside cancer cells in response to tumor-associated stimuli.

Targeted, Stimuli-Responsive, and Theranostic F Magnetic Resonance Imaging Probes.

Unlike conventional H magnetic resonance imaging (MRI), F MRI features unambiguous detection of fluorine spins due to negligible background signals. Therefore, it is considered a promising noninvasive and selective imaging method for the diagnosis of cancers and other diseases. For F MRI, fluorine-rich molecules such as perfluorocarbons (PFC) have been formulated into nanoemulsions and used as its tracer agent.

Photoactivatable BODIPY Platform: Light-Triggered Anticancer Drug Release and Fluorescence Monitoring.

We report a photoactivatable fluorophore that relies on the conversion of a dark -ester-BODIPY to an emissive -carboxylate-BODIPY. The process is triggered by the photolysis of an aryl azide to an amine, which occurs in a high photochemical yield, and does not release toxic nitroso photoproducts. Its utility is demonstrated in platforms that simultaneously release upon irradiation both a bioactive molecule and an emissive dye, resulting in an approximate 1250-fold luminescence increase.

Theranostic Nanosystems for Targeted Cancer Therapy.

Nanomaterials have revolutionized cancer imaging, diagnosis, and treatment. Multifunctional nanoparticles in particular have been designed for targeted cancer therapy by modulating their physicochemical properties to be delivered to the target and activated by internal and/or external stimuli. This review will focus on the fundamental "chemical" design considerations of stimuli-responsive nanosystems to achieve favorable tumor targeting beyond biological barriers and, furthermore, enhance targeted cancer therapy.