Nanotheranostics最新文献

{"title":"Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.","authors":"Bhanubhong Prommalee, Chalermchai Pilapong","doi":"10.7150/ntno.135510","DOIUrl":"https://doi.org/10.7150/ntno.135510","url":null,"abstract":"<p><p>Age-related keratinocyte dysfunction has been associated with altered glycosylation and dysregulated expression of several glycogenes, including <i>St6gal1</i>, <i>St3gal2</i>, and <i>Man1a</i>. Modulation of these aging-associated glycogenes may therefore represent a potential approach for investigating cellular aging phenotypes. In this study, an <i>in vitro</i> aging-like keratinocyte model exhibiting increased expression of aging-associated glycogenes was established. Antisense oligonucleotides (ASOs) targeting the upregulated glycogenes were designed and evaluated using different oligonucleotide chemistries and delivery systems. Target gene expression, lectin-based glycan profiles, Lgr6 expression, and wound closure were assessed following ASO treatment. Among the ASOs tested, phosphorodiamidate morpholino (PMO)-linked <i>Man1a</i> ASOs demonstrated greater suppression of <i>Man1a</i> mRNA than ASOs targeting <i>St6gal1</i> or <i>St3gal2</i>. Delivery of PMO-<i>Man1a</i> ASOs using milk-derived nanovesicles (NV) was associated with the greatest reduction in <i>Man1a</i> mRNA levels compared with commercial transfection reagents. Although no significant changes were detected in ConA-reactive mannose-rich glycans, treatment was associated with an increased proportion of Lgr6⁺ cells and accelerated wound closure in aging-like keratinocytes. Overall, this study provides proof-of-concept evidence that NV-mediated delivery of glycogene-targeting ASOs can modulate selected aging-associated phenotypes in keratinocytes.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"306-316"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal, Non-invasive Live Near-Infrared Fluorescence Imaging of Acute Vascularized Composite Allograft Rejection Validated by <i>Ex Vivo</i> ¹⁹F Magnetic Resonance Imaging and Histopathology.","authors":"Jelena M Janjic, Yalcin Kulahci, Fatih Zor, Sanjida Ahmed Srishti, Riddhi Vichare, Lesley M Foley, Zeynep Demir, Bedreddin Sazoğlu, Fatma Nurefsan Selek, Omer Dirican, Vidya Surti, Stefan Stratimirovic, Caitlin Crelli, Rebecca McCallin, Michele Herneisey, Huseyin Karagoz, T Kevin Hitchens, Vijay S Gorantla","doi":"10.7150/ntno.139245","DOIUrl":"https://doi.org/10.7150/ntno.139245","url":null,"abstract":"<p><p>Acute rejection remains a major cause of graft attrition in vascularized composite allotransplantation (VCA). Clinical assessment and superficial biopsy may fail to detect early or spatially heterogeneous inflammatory infiltration, particularly within deeper graft compartments. Because macrophages are among the earliest mediators of alloimmune activation, they represent an attractive target for noninvasive immune surveillance of skin-bearing grafts. We evaluated longitudinal near-infrared fluorescence (NIRF) imaging of macrophage infiltration using a perfluoro-15-crown-5 ether nanoemulsion (PCE-NE) labeled with a near-infrared fluorophore in a rat hindlimb transplantation model and a radial forearm flap model in non-human primates (NHPs). Single- and dual-dose administration strategies enabled serial visualization of macrophage recruitment and improved detection of evolving inflammatory responses during acute rejection. To capture the spatial heterogeneity of rejection, a multi-sampled region-of-interest analysis framework was developed for quantitative mapping of NIRF signal across donor and recipient tissues in rats and throughout transplanted flap regions in NHPs. To validate <i>in vivo</i> imaging findings, grafts were analyzed <i>ex vivo</i> using fluorine-19 (¹⁹F) magnetic resonance imaging, histopathology, and CD68 immunofluorescence. NIRF signal identified rejecting graft regions and demonstrated spatial patterns of inflammatory infiltration that corresponded to compartment-specific ¹⁹F MRI signal localization in <i>ex vivo</i> imaging. Imaging findings corresponded with Banff rejection grade and CD68-positive macrophage accumulation across Grade I-IV rejection. Importantly, increased NIRF and ¹⁹F MRI signals were detected during early Grade I-II rejection, when clinical manifestations remained limited. These findings establish a translational multimodal imaging strategy for longitudinal, noninvasive monitoring of acute VCA rejection and demonstrate concordance between <i>in vivo</i> NIRF imaging, <i>ex vivo</i> ¹⁹F MRI, histopathology, and immunofluorescence across rodent and non-human primate models.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"285-305"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosemary Ethanolic Extract-Loaded Electrospun Nanofibers as a Bioactive Dressing for Diabetic Wound Healing.","authors":"Rachmat Mauludin, Bintang Nurrani, Afrillia Nuryanti Garmana, Muhammad Miftahul Munir","doi":"10.7150/ntno.130423","DOIUrl":"https://doi.org/10.7150/ntno.130423","url":null,"abstract":"<p><p>Diabetic wounds are characterized by dysregulated reactive oxygen species (ROS), bacterial colonization, and excessive wound exudate. Current chronic wound management follows the TIME framework, in which infection-inflammation control and moisture balance can be addressed through wound dressings. Electrospun nanofibers incorporating plant-derived bioactives, such as rosemary ethanolic extract, offer antioxidant, antibacterial, and pro-healing properties relevant to diabetic wound therapy. In this study, rosemary ethanolic extract-loaded nanofibers were fabricated via electrospinning at 14 kV and 75% relative humidity, with a spinneret-collector distance of 13 cm, a flow rate of 1 mL/h, and a spinneret diameter of 0.83 mm. The pre-electrospinning formulation of nanofibers was evaluated for antibacterial activity by agar diffusion, also nanofiber evaluated for antioxidant activity using the DPPH radical scavenging assay and microbial penetration using <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>, and wound closure in streptozotocin-induced mice. The resulting nanofibers exhibited smooth morphology, a green appearance, and an average diameter of 237.51 ± 39.37 nm. Although the nanofibers exhibited an initial hydrophobic surface, they exhibited a high swelling capacity (481.09 ± 4.69%) indicating that water was gradually absorbed into the porous matrix and enabling substantial exudate absorption. Encapsulation efficiency was 86.17 ± 3.02%, and release kinetics followed the Korsmeyer-Peppas model. The rosemary extract-loaded formulation contained 2.067 ± 0.004 mg ascorbic acid equivalent per gram and produced inhibition zones of 20.60 ± 1.65 mm against <i>S. aureus</i> and 19.37 ± 0.64 mm against <i>S. epidermidis</i>. The electrospun nanofibers effectively prevented microbial penetration at 32°C and 37°C. <i>In vivo</i>, the wound-closure area under the curve (AUC) was significantly greater than that of the 0.9% sodium chloride control. Both unloaded cellulose acetate nanofibers and rosemary ethanolic extract-loaded cellulose acetate nanofibers promoted diabetic wound healing compared with the sodium chloride control. Although the rosemary extract-loaded nanofiber showed favorable wound healing outcomes, the present <i>in vivo</i> study did not clearly demonstrate an additional therapeutic benefit of rosemary ethanolic extract over the unloaded nanofiber.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"253-268"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal PET Imaging Reveals the Biological Fate, Pharmacokinetics, and Clearance of Zirconium-89-Labeled MXene Nanosheets <i>In Vivo</i>.","authors":"Iqra Bibi, Sairan Eom, Sang Jin Han, Kyung Jun Kang, Jung Young Kim, Sajid Mushtaq, Ji-Ae Park","doi":"10.7150/ntno.138975","DOIUrl":"https://doi.org/10.7150/ntno.138975","url":null,"abstract":"<p><p>Two-dimensional MXene (Ti₃C₂Tx) nanosheets have emerged as versatile platforms for drug delivery, photothermal and photodynamic therapy, combined chemo-photothermal treatment, and multimodal imaging including MRI and CT, as well as theranostic applications. However, their clinical translation is limited by an incomplete understanding of their long-term <i>in vivo</i> fate, pharmacokinetics, and biological interactions following systemic administration. Here, we developed a stable zirconium-89-labeled MXene platform via DFO-mediated chelation to enable quantitative, noninvasive, and longitudinal positron emission tomography (PET) imaging over 21 days. Comprehensive physicochemical characterization confirmed successful synthesis, surface functionalization, and radiolabeling of MXene nanosheets, yielding a radiochemical purity of 99.39 ± 0.66% and serum stability exceeding 97.3±1.9% over 7 days. PET/CT imaging and biodistribution studies revealed an initial pulmonary accumulation phase (30.43 ± 5.39 %ID/g), followed by progressive sequestration within the reticuloendothelial system, predominantly in the liver (maximum 30.16 ± 5.42 %ID/g on day 7) and spleen (9.31±3.17 %ID/g on day 7). Quantitative biodistribution analysis further demonstrated prolonged organ retention with gradual elimination through both renal and hepatobiliary pathways, as confirmed by excretion studies. Minimal skeletal uptake (<1.04±0.14 %ID/g throughout the study) indicated excellent <i>in vivo</i> radiolabel stability. Histopathological examination of major organs, together with <i>in vitro</i> cytotoxicity assays, revealed no significant adverse effects despite prolonged tissue retention. Collectively, these findings provide insight into the nano-bio interactions governing MXene biodistribution, organ accumulation, and clearance. More broadly, this study establishes a PET-based framework for evaluating the biological fate and safety of emerging two-dimensional nanomaterials and supports the rational development of MXene-based nanotheranostic platforms for biomedical applications.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"269-284"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing oxidative stress-responsive neuroprotective nanotheranostic agents for the image-guided treatment of radiotherapy-induced brain injury.","authors":"Saikat Maiti, Maya Teitz, Esteban Velarde, Barbara J Smith, Xiaoju Yang, Shana Lee, Kristen Lecksell, Anupama Kumari, Troy Kavanaugh Iii, Timothy Parish, Adnan Bibic, Ethel J Ngen","doi":"10.7150/ntno.138059","DOIUrl":"10.7150/ntno.138059","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Rationale: &lt;/strong&gt;Radiotherapy-induced brain injury (RIBI) is a chronic side effect, that affects up to ~90% of brain tumor survivors treated with radiotherapy. Chronic oxidative stress and neuroinflammation are key drivers of RIBI. Here, we developed oxidative stress-responsive polymeric nanotheranostic agents and evaluated their ability to reduce neuroinflammation in a preclinical mouse model of RIBI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;Two oxidative stress-responsive amphiphilic block copolymers possessing varied numbers of phenylboronic acid pinacol ester (BAPE) moieties to scavenge reactive oxygen species (ROS) were designed, synthesized, and characterized by proton and carbon-13 nuclear magnetic resonance spectroscopy. Polymer P2b was designed to have twice as many BAPE moieties as polymer P2a, for a structure-activity relationship study. The polymers were then formulated into nanoparticles and characterized using fluorescence spectroscopy, dynamic light-scattering, transmission and scanning electron microscopy, and fluorescence imaging. The ability of the agents to prevent the degradation of fluorescent R-phycoerythrin (RPE) protein under oxidative stress was also evaluated. Then, the cellular uptake and toxicity of the agents were evaluated in human umbilical vein endothelial cells (HUVECs). Next, the &lt;i&gt;in vivo&lt;/i&gt; therapeutic efficacies of the agents were evaluated in four groups of eight-week-old female BALB/c mice. Mice from one group (Group 1) were not irradiated and were used as controls, while the right brain hemispheres of mice from the other three groups were stereotactically irradiated at 80 Gy (1.7 Gy/minute). At two weeks post-irradiation, mice were intravenously treated with either a fluorescently labelled nanoparticle or phosphate buffered saline (PBS), as follows: Group 2 (PBS); Group 3 (P2a); Group 4 (P2b); and the delivery of the nanoparticles to the irradiated brain lesion was monitored with fluorescence imaging. Next, all the mice were monitored with multi-parametric magnetic resonance imaging (mp-MRI) and immunohistochemistry (CD68, IBA1, and GFAP) at 1.5 months after nanoparticle administration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Both polymers readily formed spherical nanoparticular micelles in aqueous milieu at low concentrations (~ 0.08 mg/mL), with comparable hydrodynamic diameters and zeta-potentials of 166 ± 51 nm and &lt;b&gt;-&lt;/b&gt;2.52 ± 0.658 mV for P2a; and 183 ± 54 nm and &lt;b&gt;-&lt;/b&gt;2.89 ± 1.58 mV for P2b. The activation kinetics of both nanoparticles was higher under oxidative stress than under normal physiological conditions. Additionally, both nanoparticles prevented the degradation of RPE protein under oxidative stress. Furthermore, both nanoparticles were taken up by HUVECs and did not cause any toxicity. &lt;i&gt;In vivo&lt;/i&gt;, both nanoparticles were detected in the irradiated brain lesion at 4 h after intravenous administration and retained for at least seven days post-administration. Anatomical T&lt;sub&gt;2&lt;/sub&gt;-wei","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"224-252"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Internalization, Acoustic Behavior and Stress Responses to Nanobubbles in Pancreatic Cancer Cells.","authors":"Sila Appak-Baskoy, Muhammad Saad Khan, Dhruvi Patel, Monika Lodyga, Agata A Exner, Michael C Kolios, Imogen R Coe","doi":"10.7150/ntno.130552","DOIUrl":"10.7150/ntno.130552","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, characterized by an extremely low survival rate once diagnosed. Over 90% of cases harbor activating <i>KRAS</i> mutations, which are associated with metabolic reprogramming and altered endocytic activity. New treatment modalities are urgently needed. Phospholipid-shelled, gas-filled nanobubbles (NBs) are promising ultrasound (US) contrast agents and drug delivery vehicles, with potential applications in pancreatic cancer. However, their mechanisms of cellular internalization and the resulting biological responses need to be better understood before they can be effectively utilized as theranostic agents. Here, we analyzed the internalization kinetics, endocytic pathways, acoustic responses, and cell-stress-related protein expression in perfluorocarbon-filled NBs in two pancreatic cancer cell lines: KRAS-mutant PANC-1 and KRAS wild-type BxPC-3 cells showed distinct NB uptake profiles. Flow cytometry demonstrated approximately 1.5-fold higher TR-NB uptake in PANC-1 cells compared with BxPC-3 cells, suggesting enhanced cellular association and/or intracellular retention. Higher NB signal in PANC-1 cells was accompanied by weaker and less punctate LysoTracker staining, whereas BxPC-3 cells displayed brighter, more granular acidic vesicles, suggesting differences in intracellular trafficking and compartmentalization. Pharmacological inhibition of endocytosis revealed that clathrin-mediated endocytosis contributes predominantly to uptake in BxPC-3, whereas macropinocytosis appears to play a greater role in PANC-1 cells. Upon US exposure, NBs exhibited strong initial acoustic activity that declined over time. Analysis of stress-response-associated protein expression revealed cell-specific differences: PANC-1 cells exhibited higher levels of FABP-1, HSP60, SOD2, Thioredoxin-1, and SIRT2, whereas BxPC-3 cells displayed increased COX-2 and PON-2. Collectively, our findings demonstrate that NB internalization and fate differ between PDAC subtypes, potentially reflecting cell type dependent variations in endocytic, lysosomal and adaptive pathways, underscoring the importance of developing cell-tailored nanocarrier designs to enhance delivery precision and therapeutic efficacy.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"210-223"},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Compact Non-Ionizing RF Bioelectronic Sensor for Translational Phantom-Based Detection of Tumor-Like Dielectric Changes in Bone.","authors":"Tarlan Mahouti, Hakan Yilmazer, Ladislau Matekovits, Hakan Eroğlu, Mehmet Ali Belen","doi":"10.7150/ntno.137930","DOIUrl":"10.7150/ntno.137930","url":null,"abstract":"<p><strong>Introduction: </strong>Early identification of tumor-like changes in bone remains a major diagnostic challenge because conventional imaging methods mainly rely on structural contrast and may involve ionizing radiation, high cost, or limited point-of-care accessibility. In line with the growing interest in bioelectronic and nanoelectronic biosensor technologies for translational diagnostics, this study investigates a low-cost, non-ionizing microwave sensing platform for detecting dielectric changes associated with a tumor-mimicking bone phantom.</p><p><strong>Methods: </strong>A compact microstrip resonator antenna was designed in CST Microwave Suite and fabricated on an FR4 substrate for localized near-field sensing. A multilayer bone phantom containing cortical bone- and marrow-mimicking regions was prepared using wheat flour, deionized water, dextrose, and olive oil. A separate water-rich gelatin-based tumor phantom was prepared to reproduce the higher dielectric response expected from malignant tissue. The dielectric properties of the bone and tumor phantoms were measured using a Vector Network Analyzer (VNA)-based open-ended coaxial probe system. The fabricated antenna was then experimentally evaluated by reflection coefficient (S₁₁) measurements at two healthy phantom positions and one tumor-over-phantom position.</p><p><strong>Results: </strong>Dielectric characterization confirmed a clear contrast between the bone phantom and tumor-like region in both the real and imaginary parts of relative permittivity. The tumor-loaded configuration produced a downward resonance shift of 110 MHz around 4.2-4.3 GHz, relative to the healthy reference, which was 2.75 times larger than the variation between the two healthy positions. In addition, a 4.47 dB change in S₁₁ magnitude was observed, confirming that the tumor-like inclusion altered the near-field dielectric loading and impedance-matching condition of the resonator.</p><p><strong>Conclusions: </strong>The proposed microstrip resonator antenna demonstrates the feasibility of a compact RF bioelectronic sensing approach for detecting tumor-like dielectric perturbations in a controlled bone phantom environment. Although not intended as a clinical diagnostic device at this stage, the results support further development of this platform toward translational microwave biosensing, more realistic preclinical phantoms, array-based configurations, and AI-assisted classification for future diagnostic applications.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"201-209"},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-Driven Ultrasound/Photoacoustic Theranostics for Real-Time Imaging and Therapeutics.","authors":"Praveen Kumar Annagowni, Aseem Setia, Madaswamy S Muthu","doi":"10.7150/ntno.138452","DOIUrl":"10.7150/ntno.138452","url":null,"abstract":"<p><p>Theranostic technologies that incorporate nanotechnology into ultrasound (US) and photoacoustic imaging (PAI) show great promise for the diagnosis and treatment of a wide range of diseases. Despite recent advancements in nanomaterials, US/PA systems, which use both endogenous and exogenous contrast agents, are now more sensitive and effective in therapy. Intrinsic optical absorption-based label-free imaging is made possible by endogenous agents such as collagen, lipids, haemoglobin, and melanin. Exogenous contrast agents, on the other hand, are engineered to circumvent drawbacks such as low tissue selectivity and weak signal intensity. Advanced multimodal theranostic applications are made possible by these designed nanomaterials, which improve optical absorption, acoustic responsiveness, and targeted imaging. The benefits of optical high sensitivity and acoustic deep penetration are brought together in PAI, an integrated biomedical imaging modality. It may produce structural and functional pictures with enough contrast and resolution, providing a wealth of pathology data for disease-oriented diagnostics. Consequently, it has become an effective tool of precision nanomedicine and has discovered numerous uses so far. PAI is a hybrid imaging method that uses both optical and acoustic imaging to produce detailed pictures with a wealth of information about multiple parameters. This review explains the underlying principle of US/PAI bimodal imaging techniques, including their technical benefits, contrast agents, and biomedical applications. Additionally, we go over the difficulties and potential applications of US/PAI bimodal imaging in clinical settings.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"179-200"},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Big data analytics for CLEC5A dynamics based on single cell genomics and proteomics reveal its diverse functions in human diseases.","authors":"Xiaoyuan Bai, Jingke Yao, Sarah Abdallah, Hongye Huang, Shijie Liu, Zhicheng Jin, Bingzhong Xue, Hang Shi, Zufeng Ding","doi":"10.7150/ntno.135045","DOIUrl":"10.7150/ntno.135045","url":null,"abstract":"<p><strong>Background: </strong>CLEC5A (C-type lectin domain family 5 member A) is an innate immune receptor implicated in inflammatory signaling, contributing to hyperinflammatory responses in infections and sterile inflammation. However, CLEC5A dynamics in human diseases remain to be identified. Here, we systematically characterized CLEC5A dynamics in humans across cells, tissues, and disease states, and to explore the functional significance of CLEC5A in macrophage activation based on single-cell genomics.</p><p><strong>Methods: </strong>With multi-omics (scRNA-seq, proteomics and big data analytics), we analyzed extensive human transcriptomic datasets (>42,000 samples) to profile CLEC5A expression by cell type, tissue, and disease. Single-nucleus RNA-seq (snRNA-seq) from pediatric congenital heart disease and a virtual CLEC5A gene knockout were also performed to characterize CLEC5A dynamics in humans.</p><p><strong>Results: </strong>CLEC5A is highly enriched in innate immune cells, particularly in macrophages and neutrophils. Baseline CLEC5A in most tissues is low, but it is markedly upregulated in inflammatory and infectious diseases. CLEC5A expression has sex-specific differences in certain organs. Single-cell analysis showed that CLEC5A can be considered novel marker of proinflammatory macrophages with elevated cytokine production, antigen presentation, and impaired phagocytosis. Virtual CLEC5A knockout analysis identified coordinated perturbation of immune-regulatory pathways and overlapping genes linking CLEC5A to macrophage activation networks.</p><p><strong>Conclusion: </strong>CLEC5A is predominantly expressed in myeloid cells and acts as a key amplifier of inflammation in human diseases. Our findings highlight CLEC5A as a potential biomarker and therapeutic target in myeloid-driven hyperinflammatory conditions, warranting further experimental and translational validation.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"158-178"},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles reflect senescence progression in human bone marrow-derived mesenchymal stem cells during hollow fiber bioreactor culture.","authors":"Ali Dinari, Armin M Ebrahimi, Bartosz Leszczynski, Kamil Wawrowicz, Masoud Rezaei, Maciej Słotwiński, Zenon Rajfur, Ewa L Stepien","doi":"10.7150/ntno.132088","DOIUrl":"10.7150/ntno.132088","url":null,"abstract":"<p><p>Prolonged three-dimensional culture exposes stem cells to sustain microenvironmental and mechanical stresses that can promote aging- and senescence-associated phenotypic alterations. This study examined how long-term expansion of human bone marrow-derived mesenchymal stem cells (BMSCs) in a hollow fiber bioreactor (HFB) influences cellular senescence and the molecular composition of secreted small extracellular vesicles (sEVs). During extended HFB culture, BMSCs exhibited progressive morphological flattening and cytoskeletal disorganization, accompanied by increased senescence-associated β-galactosidase activity and immunophenotypic remodeling characterized by reduced fluorescence intensity and spatial redistribution of canonical MSC markers, consistent with a stress-adapted, early senescence-associated cellular state. In parallel, sEVs were collected longitudinally over 40 days and characterized by nanoparticle tracking analysis, immunoblotting, and quantitative proteomics. While vesicle size, marker expression, and yield remained stable throughout culture, proteomic profiling revealed pronounced, phase-dependent remodeling of sEV cargo, including coordinated alterations in oxidative stress-related processes, lysosomal and extracellular matrix-associated pathways, and relative depletion of cytoskeletal and translational components. Notably, these vesicular signatures closely mirrored senescence-associated changes observed at the cellular level. The strong correspondence between cellular phenotypes and sEV proteomic profiles establishes vesicle analysis as a convergent and noninvasive readout of BMSC aging, enabling sensitive monitoring of senescence progression while reducing reliance on parallel, labor-intensive cellular assays. Collectively, these findings indicate that prolonged HFB culture promotes a controlled, stress-associated senescence program in BMSCs and position sEV proteomic profiling as a robust approach for assessing stem cell aging dynamics during long-term three-dimensional bioreactor culture.</p>","PeriodicalId":36934,"journal":{"name":"Nanotheranostics","volume":"10 ","pages":"142-157"},"PeriodicalIF":0.0,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}