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Abstract: Liver cancer is the second leading cause of cancer‐related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican‐3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3‐targeted magnetic resonance imaging, positron emission tomography, and near‐infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti‐GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Fluorescence molecular tomography (FMT) is a novel imaging modality for three-dimensional preclinical research and has many potential applications for drug therapy evaluation and tumor diagnosis. However, FMT presents an ill-conditioned and ill-posed inverse problem, which is a challenge for its tomography reconstruction. Due to the importance of FMT reconstruction, it is valuable and necessary to develop further practical reconstruction methods for FMT.Procedures: In this study, an efficient method using variable splitting strategy as well as alternating direction strategy (VSAD) was proposed for FMT reconstruction. In this method, the variable splitting strategy and the augmented Lagrangian function were first introduced to obtain an equivalent optimization formulation of the original problem. Then, the alternating direction scheme was used to solve the optimization problem and to accelerate its convergence. To examine the property of the VSAD method, three numerical simulation experiments (accuracy assessment experiment, robustness assessment experiment, and reconstruction speed assessment experiment) were performed and analyzed.Results: The results indicated that the reconstruction accuracy, the reconstruction robustness, and the reconstruction speed of FMT were satisfactory by using the proposed VSAD method. Two in vivo studies, which were conducted by using two nude mouse models, further confirmed the advantages of the proposed method.Conclusions: The results indicated that the proposed VSAD algorithm is effective for FMT reconstruction. It was accurate, robust, and efficient for FMT imaging and was feasibly applied for in vivo FMT applications. [ABSTRACT FROM AUTHOR]

Stimuli-responsive hydrogels with high strength and toughness have received great interest in recent years. In this study, temperature-responsive composite hydrogels involved the Candida antarctica lipase B were prepared by using sodium alginate and poly( N-isopropylacrylamide), and were evaluated as catalysts using the model reaction of hydrolysis of p-nitrophenol butyrate. The experimental results demonstrated that enzymatic catalyst immobilized in the thermoresponsive carriers offered possibilities for external switching and manipulation for objective reaction system. The mechanical properties of the enzyme-polymer composites pretreated by high pressure carbon dioxide could be significantly improved. The number of recycling use was significantly increased. This work provided a new approach to smart regulation for enzymatic reaction. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this work, CO2-based micelles with TMN series surfactants were used as reactive medium. Hydrolysis of p-nitrophenyl butyrate catalyzed by porcine pancreas was used as a model reaction. The reactive behaviorwas used to optimize the reaction temperature, pH, pressure, enzyme concentration and the added water. RESULTS AND DISCUSSION: Generally, the reaction parameters depended on the types of substrates and enzymes. For the hydrolysis of p-nitrophenyl butyrate in CO2-basedmicelles, the reactive yield reached a high level at temperature 303 K, system pressure 15 MPa, pH 6.8, water to surfactant ratioW0 15, and enzyme concentration 1 g mL-1. In addition, the system reactivity was highest when TMN-6 surfactant was used. CONCLUSIONS: The activity of lipase-catalyzed hydrolysis in CO2-basedmicelle was increased significantly compared with that obtained in cyclohexane oil micelle. The combination of enzyme with supercritical CO2 represented a promising 'green' reaction system for bioconversions. [ABSTRACT FROM AUTHOR]

ABSTRACT The immobilization of enzymes is one of the key issues in both the field of enzymatic research and industrialization. In this article, we report a facile method for immobilizing Candida antarctica lipase B in an alginate carrier. In the presence of calcium cations, an enzyme-alginate suspension was crosslinked to form beads with a porous structure at room temperature, and the enzymes were well dispersed in the beads. The chiral resolution of α-phenyl ethanol in the organic phase was tested by the enzyme-alginate beads. The effects of the reaction parameters, such as the enzyme concentration, temperature, and molar ratio of the substrate to the solvent, on the resolution behavior are discussed. Reuse cycle experiments for the chiral resolution of α-phenyl ethanol demonstrated that the activity of the enzyme-alginate beads was maintained without marked deactivation up to five repeated cycles. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40178. [ABSTRACT FROM AUTHOR]

Inthis work, the La-metal–organic frameworks (La-MOFs)were synthesized using lanthanum(III) nitrate and 1,3,5-benzenetricarboxylicacid (BTC) in H2O-in-1-butyl-3-methylimidazolium hexafluorophosphate(bmimPF6), bmimPF6-in-water, and the bicontinuousmicroemulsions stabilized by surfactant TX-100. The MOFs preparedwere characterized by scanning electron microscopy (SEM), transmissionelectron microscopy (TEM), powder X-ray diffraction (XRD), thermalgravimetric analysis (TGA), and FT-IR methods, and the microstructuresof the microemulsions in the H2O/bmimPF6/TX-100system were studied by small-angle X-ray scattering (SXAS) technique.It was shown that the dispersed droplets in the water-in-bmimPF6, bicontinuous and bmimPF6-in-water microemulsionswere spherical, lamellar, and cylindrical, respectively. The shapesof the La-MOFs synthesized were similar to that of the droplets inthe corresponding microemulsions. This indicated that the morphologyof MOFs could be controlled by the microstructures of the microemulsions.On the basis of the systematic experimental results, the mechanismfor controlling the morphology of the MOFs was proposed. [ABSTRACT FROM AUTHOR]

Early diagnosis can effectively improve the survival of glioblastoma multiforme (GBM). A specific imaging technique that is simultaneously deep penetrating and sensitive to small tissue changes is desired to identify GBM. Due to its excellent features in signal contrast, detection sensitivity, and none or little attenuation in tissue, magnetic particle imaging (MPI) possesses great potential in cancer diagnosis, especially when the imaging modality is equipped with specifically targeted nanoprobes. However, when gliomas are small, the blood–brain barrier (BBB) is complete and prevents nanoprobes from entering the brain, which negates the theranostic effect. This study proposes a biomimetic nanoplatform that assist the MPI tracers in breaking through the BBB and then demonstrate a targeted and sensitive diagnosis of GBM. Afterward, the photothermal therapy and immune regulation show an excellent therapeutic effect on the GBM. It is experimentally confirmed that the MPI signal does not decay with tissue depth and shows excellent sensitivity for thousands‐cells. Only small animals are conducted in this study due to the limitations of the current commercial MPI scanner, however, this research theoretically enables large animal and human studies, which encourages a promising pathway toward the noninvasive diagnosis of early‐stage GBM in clinics. [ABSTRACT FROM AUTHOR]

The Maillard reaction (MR) of tilapia byproduct protein hydrolysates was investigated for the use of byproduct protein as a food ingredient and to mask its fishy odor and bitter flavor. The flavor differences in tilapia byproduct hydrolysates before and after the MR were analyzed to explore the key flavor precursor peptides and amino acids involved in MR. The results suggested that eight key volatile substances, including 2,5‐dimethylpyrazine, 2‐pentylfuran, hexanal, octanal, nonanal, (E)‐2‐decenal, decanal, and 1‐octen‐3‐ol contributed most to the MR products group (ROAV > 1). Ten volatile compounds, including 1‐octen‐3‐ol, hexanal, 2‐pentylfuran, 2,5‐dimethylpyrazine, methyl decanoate, and 2‐octylfuran, were the flavor markers that distinguished the different samples (VIP > 1). The four most consumed peptides were VAPEEHPTL, GPIGPRGPAG, KSADDIKKAF, and VWEGQNIVK. Umami peptides and bitter free amino acids (FAAs) were the key flavor precursor peptide and FAAs, respectively. Overall, the hydrolysates of tilapia byproducts with flavor improved by MR are a promising strategy for the production of flavorings. [ABSTRACT FROM AUTHOR]

Real-time renal imaging is indispensable for monitoring kidney-related disease processes and evaluating the nephrotoxicity of nanoprobes. Owing to their small size, tunable photoluminescence properties, and low biotoxicity, carbon dots (CDs) are widely employed as nanoprobes for imaging-guided disease diagnosis. However, the preparation of near-infrared CDs is a stupendous challenging. Here, CDs with near-infrared fluorescence (NIR-CDs) were prepared by one-pot pyrolysis and were comprehensively evaluated for real-time renal imaging. The NIR-CDs possessed super-small size (1.8 ± 0.2 nm) and high quantum yield (14.3% in aqueous solution) at 696 nm. NIR-CDs exhibited high-efficiency renal clearance at 24 h post-treatment (97.47–99.27% ID) via glomerular filtration. The irreversible clearance of NIR-CDs enables effective real-time monitoring of kidney function in the normal and acute kidney injury (AKI) mouse models. Consequently, NIR-CDs can be utilized for imaging analyses of impaired kidney function, pioneering a serviceable guideline for neoapplications of NIR-CDs. [Display omitted] [ABSTRACT FROM AUTHOR]

Stored food is susceptible to deterioration owing to oxidation, endogenous enzymes, and microbial action. Proteins extracted from aquatic plants and animals have attracted attention as alternatives to chemical preservatives because of their antimicrobial, antioxidant, antifreeze, and excellent mechanical properties, rendering them highly promising active ingredients in the field of food preservation. The type and molecular structure of proteins affect their preservation mechanisms and effectiveness. Therefore, this review summarizes different proteins extracted from aquatic plants and animals for food preservation applications, as well as their application background, structure-technofunctional properties relationship , and mode of application. Aquatic-derived proteins are effective in mitigating the quality deterioration of food products owing to their good food preservation properties and storage quality control. Furthermore, the challenges faced by aquatic-derived proteins in the current research and their application in food preservation are discussed, considering the commercial economic benefits and current development of the food industry and the future direction of their development. This review provides guidance on the application of aquatic-derived proteins in food preservation and a theoretical basis for future research. • Aquatic-derived proteins have preservation properties and storage quality control. • Collagen, gelatin and myofibrillar protein have film-forming mechanical properties. • Microalgae protein has antioxidant activity removing free radicals and chelates metal ions. • Antimicrobial peptide inhibits bacterial through electrostatic & hydrophobic interactions. • Antifreeze protein improves low-temperature preservation by thermal hysteresis activity. [ABSTRACT FROM AUTHOR]

• More umami and sweet, and less bitter AAs generated by oxidized lipids and cysteine. • Six unsaturated fatty acids were identified as potential flavor precursors. • More aldehydes, some ketones, esters and less hydrocarbons contribute to aroma. • 13 key volatile compounds were identified as affecting the overall odour. • Lipid oxidation, degradation and Maillard reaction are the main reaction for soup. Deodorization and umami enhancement are important challenges in promoting and consuming fish products. The aim of this study was to establish whether exogenous addition of oxidized lipids and cysteine can improve the fishy, umami and create a characteristic flavor in tilapia fish head soup. The results revealed that adding oxidized lipids and cysteine enhanced the sensory attributes of fish head soup and promoted the production of pleasant-tasting amino acids and fewer bitter amino acids in the Maillard reaction. Additionally, the combination increased the levels of well-flavored aldehydes, esters, heterocyclic compounds and less hydrocarbons in the fish head soup. Among the 13 volatile compounds screened, nine were identified as characteristic aromas of fish head soup, including nonanal, (E,E)-2,4-decadienal, 1-octen-3-ol, (E)-2-decenal, acetic acid, hexanal, heptanal, 2-octenal, and decanal. Exogenous lipid oxidation products, fatty acid oxidation, and Maillard reaction can improve the aroma and umami of tilapia fish head soup. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polyphenols with more hydroxyl groups have stronger binding to bovine serum albumin. • Polyphenols improve the wettability of bovine serum albumin by hydrogen bonding. • The stability of high internal phase Pickering emulsion improved by polyphenols. Protein-polyphenol colloidal particles are promising stabilizers for high internal phase Pickering emulsions (HIPPEs). However, the relationship between the structure of the polyphenols and its ability to stabilize HIPPEs has not been studied thus far. In this study, bovine serum albumin (BSA)-polyphenols (B-P) complexes were prepared, and their ability to stabilize HIPPEs was investigated. The polyphenols were bound to BSA via non-covalent interactions. Optically isomeric polyphenols formed similar bonds with BSA, whereas a greater number of trihydroxybenzoyl groups or hydroxyl groups in the dihydroxyphenyl moieties of polyphenols increased the B-P interactions. Polyphenols also reduced the interfacial tension and enhanced the wettability at the oil–water interface. The HIPPE stabilized by BSA-tannic acid complex exhibited the highest stability among the B-P complexes and resisted demixing and aggregation during centrifugation. This study promotes the potential applications of polyphenol-protein colloidal particles-stabilized HIPPEs in the food industry. [ABSTRACT FROM AUTHOR]

Disturbances in intracellular copper (Cu) homeostasis can trigger cuproptosis, a new form of cell death, which, when combined with photothermal therapy (PTT), offers a promising solution to the persistent challenges in colorectal cancer (CRC) treatment. In this study, a "three-level nanoparticle rocket" strategy is developed by engineering Cu 5.4 O, a multifunctional Cu-based nanoenzyme that is photothermal and has electron transfer properties and antioxidant efficiency. Cu 5.4 O effectively remodels the inflammatory environment by scavenging reactive oxygen species, thereby overcoming the traditional limitations of PTT. Concurrently, Cu 5.4 O releases substantial amounts of Cu + into malignant cells, disrupting Cu homeostasis, inducing cuproptosis, and ultimately inhibiting tumor progression. In vivo and in vitro experiments demonstrate that Cu 5.4 O operates through multiple successive and interlocking stages to significantly eradicate tumors, prevent relapse, and prolong survival. This study provides profound insights into the synergistic effects of PTT, inflammatory regulation, and cuproptosis within the complex tumor microenvironment, presenting innovative approaches for future CRC therapy., (© 2025 Wiley‐VCH GmbH.)

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn 3 O 4 nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn 3 O 4 NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn 3 O 4 NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn 3 O 4 protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

Purpose: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity., Methods: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues., Results: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%., Conclusion: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a respiratory illness, characterized by symptoms such as fever, dry cough, and drowsiness. This virus is highly contagious, has significant mutation rates, and induces infection despite vaccination. Its widespread prevalence has profoundly impacted global economies, societies, and daily life. In response to these challenges, researchers have committed themselves to advancing rapid and cost-effective diagnostic technologies, holding substantial importance for the rapid evolution of global diagnostic capabilities. Nonetheless, various detection methods diverge in principles, sensitivity, specificity, and other aspects. Additionally, COVID-19 is not an isolated event, but part of a broader history of pandemics in human society. Therefore, this article briefly reviews the existing detection methods of SARS-CoV-2, providing valuable technical insights to diagnose not only SARS-CoV-2 but also other viruses., Methods: A search was conducted on PubMed by utilizing keywords such as "SARS-CoV-2 detection", "RT-qPCR detection for SARS-CoV-2", "LFA detection for SARS-CoV-2", "Biosensors detection for SARS-CoV-2", and similar terms. The objective was to compile and summarize relevant articles on these topics., Results: Currently, the real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) stands as a widely employed method for detecting SARS-CoV-2, enabling an accurate detection of viral RNA. Furthermore, the lateral flow assay (LFA) assists in detecting viral antigens and antibodies. Gene sequencing technology primarily facilitates the real-time monitoring of mutated SARS-CoV-2 strains, while biosensors could offer a rapid, economical, sensitive, and precise detection of SARS-CoV-2. These methods provide a strong technical support for the early detection and diagnosis of SARS-CoV-2., Conclusions: This paper offers a concise overview of pathogen detection methods, as molecular biology, and immunological detection techniques, alongside emerging biosensor platforms relevant to SARS-CoV-2, and delineates the strengths and weaknesses of each method.

Background: Prostate cancer (PCa) is the most prevalent cancer among males, emphasizing the critical need for precise diagnosis and treatment to enhance patient prognosis. Recent studies have extensively utilized urine exosomes from patients with cancer for targeted delivery. This study aimed to employ highly sensitive magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor the targeted delivery of an exosome-loaded platform at the tumour site, offering insights into a potential combined photothermal and magnetic thermal therapy regime for PCa., Results: MPI and FMI were utilized to monitor the in vivo retention performance of exosomes in a prostate tumour mouse model. The exosome-loaded platform exhibited robust homologous targeting ability during imaging (SPIONs@EXO-Dye:66·48%±3·85%; Dye-SPIONs: 34·57%±7·55%, **P<0·01), as verified by in vitro imaging and in vitro tissue Prussian blue staining., Conclusions: The experimental data underscore the feasibility of using MPI for in vivo PCa imaging. Furthermore, the exosome-loaded platform may contribute to the precise diagnosis and treatment of PCa., (© 2024. The Author(s).)

Effect of complexation of three medium-chain fatty acids (octanoic, decylic and lauric acid, OA, DA and LA, respectively) on structural characteristics, physicochemical properties and digestion behaviors of cassava starch (CS) was investigated. Current study indicated that LA was more easily to combine with CS (complex index 88.9%), followed by DA (80.9%), which was also consistent with their corresponding complexed lipids content. Following the investigation of morphology, short-range ordered structure, helical structure, crystalline/amorphous region and fractal dimension of the various complexes, all cassava starch-fatty acids complexes (CS-FAs) were characterized with a flaked morphology rather than a round morphology in native starch (control CS). X-ray diffraction demonstrated that all CS-FAs had a V-type crystalline structure, and nuclear magnetic resonance spectroscopy confirmed that the complexes made from different fatty acids displayed similar V6 or V7 type polymorphs. Interestingly, small-angle X-ray scattering analysis revealed that α value became greater following increased carbon chain length of fatty acids, indicating the formation of a more ordered fractal structure in the aggregates. Changes in rheological parameters G' and G'' indicated that starch complexed with fatty acids was more likely to form a gel network, but difference among three CS-FAs complexes was significant, which might be contributed to their corresponding hydrophobicity and hydrophilicity raised from individual fatty acids. Importantly, digestion indicated that CS-LA complexes had the lowest hydrolysis degree, followed by the greatest RS content, indicating the importance of chain length of fatty acids for manipulating the fine structure and functionality of the complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Tilapia produces a large number of by-products during processing, which contain potentially flavorful peptides., Methods: The application of PyRx software enabled batch molecular docking andscreening of 16 potential salty peptides from 189 peptides identified in the enzymaticdigestion of tilapia by-products., Results: According to sensory analysis, all 16 peptides werepredominantly salty with a threshold of 0.256 - 0.379 mmol/L with some sournessand astringency, among which HLDDALR had the highest salty intensity, followedby VIEPLDIGDDKVR, FPGIPDHL, and DFKSPDDPSRH. I addition, moleculardocking results showed these four core peptides with high salt intensity bound to thesalt receptor TRPV1 mainly via van der Waals interactions, hydrogen bonds, andhydrophobic forces; Arg491, Tyr487, VAL441, and Asp708 were the key sites for thebinding of salty peptides to TRPV1. Therefore, the application of batch moleculardocking using PyRx is effective and economical for the virtual screening of saltypeptides., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Zhou, Fu, Feng, Wang, Li, Xia, Shang and He.)

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer., Results: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor "cruise missile", mesoporous Fe 3 O 4 -containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment., (© 2022. The Author(s).)

Pro-tumoral and immunosuppressive M2-like tumor-associated macrophages (TAMs) contribute to tumor progression, recurrence and distal metastasis. However, current TAMs-modulating therapeutic strategies often encounter challenges including insufficient immune activation, weak antigen presentation ability and unsatisfactory antitumor immune performance. Herein, cyclic RGD peptide functionalized and manganese doped eumelanin-like nanocomposites (RMnMels) are reported for combined hyperthermia-immunotherapy against PC3 prostate cancer. The RMnMels could promote M2-to-M1 macrophage repolarization via scavenging multiple reactive oxygen species and remodeling the immunosuppressive tumor microenvironment. Following near-infrared light irradiation, RMnMels-mediated thermal ablation not only could destroy tumor cells directly, but also elicit the release of damage associated molecular patterns and tumor-associated antigens, provoking robust tumor immunogenicity and strong antitumor immune responses. The results showed that RMnMels could effectively scavenge reactive oxygen species and promote M2-to-M1 macrophage repolarization both in vitro and in vivo. Synergistically enhanced anti-tumor therapeutic efficacy was achieved following single administration of RMnMels plus single round of laser irradiation, evidenced by decreased primary tumor sizes and decreased number of distant liver metastatic nodules. The as-developed RMnMels may represent a simple and high-performance therapeutic nanoplatform for immunomodulation and enhanced antitumor immune responses., (© 2022. The Author(s).)

Purpose: Pancreatic cancer is still associated with a poor outcome and low patient quality of life, which are mainly attributed to the late detection and requirement of distal pancreatectomy with extended resection of pancreatic tumors. Therefore, novel strategies for early screening and precise tumor resection are urgently needed. In this study, we evaluated the feasibility of a low-density lipoprotein receptor (LDLR)-targeted small-molecule contrast agent (peptide-22-Cy7) for early screening with photoacoustic tomography and near-infrared (NIR) imaging as guided surgical navigation to achieve precise resection., Procedure: Normal pancreatic cells (HPDE6-C7) and cancer cells (PANC-1) were respectively used in the in vitro targeting evaluations. The ability of peptide-22-Cy7 for preoperative in vivo pancreatic tumor detection was investigated in a mouse orthotopic pancreatic cancer model (n = 10) using photoacoustic tomography; 18 tumor-bearing mice were further divided into three groups for different treatments. After intravenous injection of peptide-22-Cy7, surgical navigation was conducted through laparotomy. Histopathological analysis was used to further confirm the tumor area and the state of surgical margins., Results: Flow cytometry demonstrated that peptide-22 is highly specific to pancreatic cancer cells, with a fluorescence intensity of approximately 87.3 %. Orthotopic pancreatic tumors with a size of 4 mm could be accurately detected by photoacoustic tomography. Surgical navigation effectively achieved R0 resection and minimized the range of resection, which led to increased body weight of the mice following surgery., Conclusion: Overall, our newly developed targeted contrast agent facilitated the accurate positioning and resection of pancreatic tumors. Photoacoustic tomography and optical imaging-guided surgical navigation may be a novel direction for improving the survival, quality of life, and disease management of pancreatic cancer patients.

Single instillation (SI) reduces recurrence of non-muscle-invasive bladder cancer by chemoresecting floating tumor cells and residual tumor lesions (RTLs) after transurethral resection of the bladder, but with limited efficacy. Current studies improved this by prolonging retention time and increasing penetration to bladder wall, ignoring that the two separate factors should be treated in different ways. Here, we introduced a smart gel system-based SI to prevent re-implantation of tumor cells (RTCs) and ablate RTLs in a "divide-and-rule" approach. The gel system was synthesized by PEG-PAMAM and dextran aldehyde and composed of gold nanorods and gemcitabine for photothermal therapy and chemotherapy, respectively. It was developed to provide dextran aldehyde-selective adhesion with tissue amines. Since tumor surface expressed high levels of collagen, the exposed amines could act as adhesion points for the gel system. Thus, the gel presented more affinity to tumor tissues. When being instilled, it could form a protective layer on the inner face of the entire bladder wall immediately, preventing RTCs in early time. And it persisted long at the tumor site, ablating RTLs. Our data proved the gel system improved intravesical treatment efficacy in a "divide-and-rule" approach and might be a promising treatment strategy for SI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: The diagnosis and treatment of hepatocarcinoma (HCC) is believed to be improved due to the development of specific targeting probes by molecular imaging methods. GPC3, which is a hepatocellular carcinoma (HCC)-specific tumor marker, anchors at most HCC cells. To target this cell membrane protein, we developed a novel nanoparticle by conjugating WS 2 -Ga 3+ -PEG and a short peptide with favorable specificity and affinity to the GPC3 protein. Materials & methods: In in vitro assay, several physical properties of the novel probe were evaluated. In in vivo assay, MRI, photoacoustic imaging and photothermal therapy were performed in the subcutaneous HepG2-bearing mice with the novel probe. Results & conclusion: The effect of imaging and photothermal therapy was significant. We revealed that the novel nanosheet WS 2 -Ga 3+ -PEG-peptide is promising to detect and treat HCC-expressing GPC3.