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45 pages, 1751 KB  
Review
Exploring the Role of Extracellular Vesicles in Pancreatic and Hepatobiliary Cancers: Advances Through Artificial Intelligence
by Eleni Myrto Trifylli, Athanasios Angelakis, Sotirios P. Fortis, Anastasios G. Kriebardis, Nikolaos Papadopoulos, Evangelos Koustas, Panagiotis Sarantis, Michalis V. Karamouzis, Spilios Manolakopoulos and Melanie Deutsch
Int. J. Mol. Sci. 2026, 27(3), 1524; https://doi.org/10.3390/ijms27031524 - 4 Feb 2026
Viewed by 57
Abstract
Gastrointestinal (GI) cancers constitute an umbrella term for a wide variety of malignancies that are located in the digestive tract (esophageal, gastric, small and large intestine, anus, liver, gallbladder, and pancreas), with 25% of total cancers and 35% of cancer-related deaths being attributed [...] Read more.
Gastrointestinal (GI) cancers constitute an umbrella term for a wide variety of malignancies that are located in the digestive tract (esophageal, gastric, small and large intestine, anus, liver, gallbladder, and pancreas), with 25% of total cancers and 35% of cancer-related deaths being attributed to them. An alarming trend of rising GI malignancy diagnoses, especially in younger age groups, underscores the need for discoveries in liquid-based biomarkers that facilitate both early detection and optimal disease management. Extracellular vesicles (EVs) not only constitute promising nano-sized biomarkers, but also, via bioengineering, have shown a great therapeutic potential, with artificial intelligence (AI) revolutionizing their research via the selection of the best biomarkers from omics, the recognition of pathophysiological patterns, and facilitating a faster drug-development via AI-driven EV engineering, drug delivery modeling, and target identification. In this review, we will provide a clear insight into the implementation of AI methodologies in EV-based biomarker discovery and therapeutics for pancreatic and hepatobiliary cancer. Full article
25 pages, 1620 KB  
Review
Wearable Sensors for Health Monitoring
by Caroline Abreu, Carla Bédard, Jean-Christophe Lourme and Benoit Piro
Biosensors 2026, 16(2), 93; https://doi.org/10.3390/bios16020093 - 2 Feb 2026
Viewed by 338
Abstract
The growing global population and the rapid increase in older adults are driving healthcare costs upward. In response, the healthcare system is shifting toward models that enable continuous monitoring of individuals without requiring hospital admission. Advances in sensing technologies, embedded systems, wireless communication, [...] Read more.
The growing global population and the rapid increase in older adults are driving healthcare costs upward. In response, the healthcare system is shifting toward models that enable continuous monitoring of individuals without requiring hospital admission. Advances in sensing technologies, embedded systems, wireless communication, nanotechnology, and device miniaturization have made these smart systems possible. Wearable sensors can monitor physiological indicators and other symptoms, helping to detect unusual or unexpected events. This allows for the provision of timely assistance when it is needed most. This paper outlines the challenges associated with these systems and reviews recent developments in wearable, sensor-based human activity monitoring. The focus is on health monitoring applications, including relevant biomarkers, wearable and implantable sensors, and established sensor technologies currently used in healthcare, as well as future prospects. It also discusses the challenges involved in researching, developing, and applying these sensors. The goal is to promote the widespread use of these sensors in human health monitoring. Full article
(This article belongs to the Special Issue Sensors for Human and Animal Health Monitoring)
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21 pages, 1585 KB  
Review
Nano–Micronutrients of Iron and Copper for Improved Human Nutrition: A Narrative Review
by Lok R. Pokhrel, Sina Fallah and Lauren C. Garcia
Appl. Sci. 2026, 16(3), 1478; https://doi.org/10.3390/app16031478 - 2 Feb 2026
Viewed by 92
Abstract
Micronutrient deficiencies of iron and copper are global challenges that significantly undermine public health, particularly among vulnerable populations. Recent advancements in nanotechnology have paved the way for nano–micronutrient formulations that offer improved nutrient delivery over conventional supplements. Nano–micronutrients leverage sub-100 nm particle sizes, [...] Read more.
Micronutrient deficiencies of iron and copper are global challenges that significantly undermine public health, particularly among vulnerable populations. Recent advancements in nanotechnology have paved the way for nano–micronutrient formulations that offer improved nutrient delivery over conventional supplements. Nano–micronutrients leverage sub-100 nm particle sizes, increased-surface area, and controlled-release mechanisms to enhance gastrointestinal absorption and bioavailability of iron and copper. This narrative review takes a nuanced approach to critically evaluate published literature comparing nano-formulations with traditional supplements, demonstrating that nano–micronutrients enable targeted cellular uptake, reduce interactions with anti-nutritional factors, and improve organoleptic properties of fortified foods. Evidence indicates that these formulations can markedly elevate clinical biomarkers such as serum ferritin and hemoglobin, while reducing required dosages and mitigating gastrointestinal side effects. However, challenges persist regarding long-term safety, production scalability, and regulatory oversight. Public acceptance remains contingent on transparent safety assessments and effective communication of benefits. Future research should focus on standardizing synthesis methods, developing green production processes, and integrating robust in vitro and in vivo models to elucidate long-term health impacts. Overall, nano–micronutrients of iron and copper hold transformative potential to alleviate micronutrient deficiencies and improve human nutrition, provided technical and regulatory challenges are adequately addressed. Full article
(This article belongs to the Special Issue Diet, Nutrition and Human Health)
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32 pages, 2622 KB  
Review
Recent Advances in Nanoparticle-Based Drug Delivery Strategies to Cross the Blood–Brain Barrier in Targeted Treatment of Alzheimer’s Disease
by Hoa Le, Giang T. T. Vu, Amos Abioye and Adeboye Adejare
Pharmaceutics 2026, 18(2), 192; https://doi.org/10.3390/pharmaceutics18020192 - 1 Feb 2026
Viewed by 204
Abstract
The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses [...] Read more.
The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses and therapeutic failure in the treatment of Alzheimer’s disease (AD). However, the advent of nanotechnology has provided significant solutions to the BBB challenges, enabling particle size reduction, enhanced drug solubility, reduced premature drug degradation, extended and sustained drug release, enhanced drug transport across the BBB, increased drug target specificity and enhanced therapeutic efficacy. In corollary, a library of brain-targeted surface-functionalized nanotherapeutics has been widely reported in the current literature. These promising in vitro, in vivo and pre-clinical results from the existing literature provide quantitative evidence for the relative clinical utility of each of the techniques, indicating remarkable capacity for brain-targeted carrier systems; many of them are still being tested in human clinical trials. However, despite the recorded research successes in drug transport across the BBB, there are currently no clinically proven medications that can slow or reverse the progression of AD because most of the novel therapeutics have not been successful during the clinical trials. Therefore, the main option for the treatment of AD is symptomatic treatment using cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Although these therapies help to alleviate symptoms of AD and improve patients’ quality of life, they neither slow the progression of disease nor cure it. Thus, an effective disease-modifying therapy for the treatment of AD is an unmet clinical need. It is apparent that a deeper understanding of the structural complexity and controlling dynamic functions of the BBB in tandem with a comprehensive elucidation of AD pathogenesis are crucial to the development of novel nanocarriers for the effective treatment of AD. Therefore, this narrative review describes the contextual analysis of several promising strategies that enhance brain-targeted drug delivery across the BBB in AD treatment and recent research efforts on two major AD biomarkers that have revolutionized AD diagnosis, amyloid-beta plaques and phosphorylated tau protein tangle, as potential targets in AD drug development. This has led to the Food and Drug Administration (FDA)’s approval of two intravenous (IV) anti-amyloid monoclonal antibodies, Lecanemab (Leqembi®) and Donanemab (Kisunla®), which were developed based on the Aβ cascade hypothesis for the treatment of early AD. This review also discusses the recent shift in the Aβ cascade hypothesis to Aβ oligomer (conformer), a soluble intermediate of Aβ, which is the most toxic mediator of AD and could be the most potent drug target in the future for a more accurate and effective drug development model for the treatment of AD. Furthermore, various promising nanoparticle-based drug carriers (therapeutic nanoparticles) that were developed from intensive research are discussed, including their clinical utility, challenges and prospects in the treatment of AD. Overall, it suffices to state that the advent of nanotechnology provided several innovative techniques for overcoming the BBB and improving drug delivery to the brain; however, their long-term biosafety is a relevant concern. Full article
(This article belongs to the Special Issue Smart Polymeric Nanoparticle-Based Drug Delivery Systems)
27 pages, 890 KB  
Review
Nanotechnology-Enabled Precision Therapy for Lung Cancer in Never-Smokers
by Cristian Cojocaru, Adina Magdalena Țurcanu, Ruxandra Cojocaru and Elena Cojocaru
Pharmaceutics 2026, 18(2), 161; https://doi.org/10.3390/pharmaceutics18020161 - 26 Jan 2026
Viewed by 218
Abstract
Lung cancer in never-smokers (LCINS) represents a distinct clinical entity driven by dominant oncogenic alterations and characterized by a low tumor mutational burden. Although tyrosine kinase inhibitors (TKIs) achieve high initial response rates, their long-term efficacy is limited by suboptimal pharmacokinetics, restricted central [...] Read more.
Lung cancer in never-smokers (LCINS) represents a distinct clinical entity driven by dominant oncogenic alterations and characterized by a low tumor mutational burden. Although tyrosine kinase inhibitors (TKIs) achieve high initial response rates, their long-term efficacy is limited by suboptimal pharmacokinetics, restricted central nervous system (CNS) penetration, tumor microenvironment barriers, and acquired resistance. In this review, we critically assess the current state of nanotechnology-assisted drug delivery systems for LCINS, with a primary focus on how rationally designed nanocarriers can overcome biological barriers, enable molecular subtype-specific therapeutic strategies, and address mechanisms that limit clinical efficacy and durability of response. We conducted a structured literature search using PubMed and Web of Science (January 2022 to November 2025), focusing on primary studies reporting the preparation, physicochemical properties, and therapeutic performance of nanocarriers in in vitro and in vivo models, as well as available pharmacokinetic and clinical data. LCINS is characterized by inefficient vasculature, high extracellular matrix density, active efflux transporters, and immunosuppressive niches, and is frequently complicated by brain metastases. Nanocarrier-based platforms can enhance aqueous solubility, prolong systemic circulation, and improve tumor or CNS targeting. Co-delivery systems combining TKIs with nucleic acid-based therapeutics, together with stimuli-responsive platforms, offer the potential for simultaneous modulation of multiple oncogenic pathways and partial mitigation of resistance mechanisms. In summary, nanotechnology provides a promising strategy to improve both the efficacy and specificity of targeted therapies in LCINS. Successful clinical translation will depend on biologically aligned carrier–payload combinations, scalable and reproducible manufacturing processes, and biomarker-guided patient selection. Full article
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43 pages, 1125 KB  
Review
A Decade of Innovation in Breast Cancer (2015–2025): A Comprehensive Review of Clinical Trials, Targeted Therapies and Molecular Perspectives
by Klaudia Dynarowicz, Dorota Bartusik-Aebisher, Sara Czech, Aleksandra Kawczyk-Krupka and David Aebisher
Cancers 2026, 18(3), 361; https://doi.org/10.3390/cancers18030361 - 23 Jan 2026
Viewed by 338
Abstract
The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as [...] Read more.
The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article
(This article belongs to the Section Cancer Therapy)
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58 pages, 2014 KB  
Review
FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies
by Zijie He, Yizhen Chen, Genglin Li, Jintao Wang, Yuxin Wang, Pengjie Tu, Yangyun Huang, Lilan Zhao, Xiaojie Pan, Hengrui Liu and Wenshu Chen
Cancers 2026, 18(1), 89; https://doi.org/10.3390/cancers18010089 - 27 Dec 2025
Viewed by 574
Abstract
Aberrations in fibroblast growth factor receptors (FGFRs) constitute a key oncogenic mechanism across multiple solid tumors, influencing tumor initiation, therapeutic response, and clinical outcomes. This review synthesizes current knowledge on the molecular biology, signaling networks, and tumor-specific distribution of FGFR alterations, including amplifications, [...] Read more.
Aberrations in fibroblast growth factor receptors (FGFRs) constitute a key oncogenic mechanism across multiple solid tumors, influencing tumor initiation, therapeutic response, and clinical outcomes. This review synthesizes current knowledge on the molecular biology, signaling networks, and tumor-specific distribution of FGFR alterations, including amplifications, point mutations, and gene fusions. The mechanistic basis of FGFR-driven tumor progression is discussed, including activation of downstream signaling pathways, crosstalk with other receptor tyrosine kinases, and regulation of the tumor microenvironment, angiogenesis, and immune escape. Recent development of selective FGFR inhibitors—such as pemigatinib, erdafitinib, and futibatinib—has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. However, acquired resistance remains a major challenge, driven by secondary mutations, activation of bypass pathways, and intratumoral heterogeneity. Integration of multi-omics profiling, liquid biopsy monitoring, and biomarker-guided patient selection is essential to optimize therapeutic efficacy and overcome resistance. This review also highlights emerging therapeutic modalities, such as antibody–drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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47 pages, 10163 KB  
Review
Nanomedicine in Ovarian Cancer: Advances in Imaging, Targeted Delivery, and Theranostic Therapeutic Platforms
by Dorota Bartusik-Aebisher, Izabella Wilk and David Aebisher
Cancers 2026, 18(1), 86; https://doi.org/10.3390/cancers18010086 - 27 Dec 2025
Viewed by 753
Abstract
Ovarian cancer continues to be the most lethal gynaecological malignancy, principally due to its late-stage diagnosis, extensive peritoneal dissemination, chemoresistance, and limitations of current imaging and therapeutic strategies. By optimising pharmacokinetics, refining tumour-selective drug delivery, and supporting high-resolution, multimodal imaging, nanomedicine offers a [...] Read more.
Ovarian cancer continues to be the most lethal gynaecological malignancy, principally due to its late-stage diagnosis, extensive peritoneal dissemination, chemoresistance, and limitations of current imaging and therapeutic strategies. By optimising pharmacokinetics, refining tumour-selective drug delivery, and supporting high-resolution, multimodal imaging, nanomedicine offers a versatile platform to address these limitations. In this review, current progress across lipid-based, polymeric, inorganic, hybrid, and biomimetic nanocarriers is synthesised, emphasising how tailored physiochemical properties, surface functionalisation, and stimuli-responsive designs can improve tumour localisation, surmount stromal and ascetic barriers, and enable controlled drug release. Concurrently, significant advancement in imaging nanoprobes, including magnetic resonance imaging (MRI), positron emission tomography (PET)/single-photon emission computed tomography (SPECT), optical, near-infrared imaging (NIR), ultrasound, and photoacoustic systems, has evolved early lesion detection, intraoperative guidance, and quantitative monitoring of treatment. Diagnosis and therapy are further integrated within single platforms by emerging theranostic constructs, encouraging real-time visualisation of drug distribution and treatment response. Additionally, immune-nanomedicine, intraperitoneal depot systems, and nucleic acid-centred nanotherapies offer promising strategies to address immune suppression and molecular resistance in advanced ovarian cancer. In spite of noteworthy achievements, clinical translation is limited by complex manufacturing requirements, challenges with safety and stability, and restricted patient stratification. To unlock the full clinical potential of nanotechnology in ovarian cancer management, constant innovation in scalable design, regulatory standardisation, and integration of precision biomarkers will be necessary. Full article
(This article belongs to the Section Methods and Technologies Development)
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43 pages, 1898 KB  
Review
Advances in Colorectal Cancer: Epidemiology, Gender and Sex Differences in Biomarkers and Their Perspectives for Novel Biosensing Detection Methods
by Konstantina K. Georgoulia, Vasileios Tsekouras and Sofia Mavrikou
Pharmaceuticals 2026, 19(1), 13; https://doi.org/10.3390/ph19010013 - 20 Dec 2025
Viewed by 1112
Abstract
Colorectal cancer (CRC) remains a major cause of morbidity and mortality worldwide, with its incidence and biological behavior influenced by both genetic and environmental factors. Emerging evidence highlights notable sex differences in CRC, with men generally exhibiting higher incidence rates and poorer prognoses, [...] Read more.
Colorectal cancer (CRC) remains a major cause of morbidity and mortality worldwide, with its incidence and biological behavior influenced by both genetic and environmental factors. Emerging evidence highlights notable sex differences in CRC, with men generally exhibiting higher incidence rates and poorer prognoses, while women often display stronger immune responses and distinct molecular profiles. Traditional screening tools, such as colonoscopy and fecal-based tests, have improved survival through early detection but are limited by invasiveness, cost, and adherence issues. In this context, biosensors have emerged as innovative diagnostic platforms capable of rapid, sensitive, and non-invasive detection of CRC-associated biomarkers, including genetic, epigenetic, and metabolic alterations. These technologies integrate biological recognition elements with nanomaterials, microfluidics, and digital systems, enabling the analysis of biomarkers such as proteins, nucleic acids, autoantibodies, epigenetic marks, and metabolic or VOC signatures from blood, stool, or breath and supporting point-of-care applications. Electrochemical, optical, piezoelectric, and FET platforms enable label-free or ultrasensitive multiplexed readouts and align with liquid biopsy workflows. Despite challenges related to standardization, robustness in complex matrices, and clinical validation, advances in nanotechnology, multi-analyte biosensing with artificial intelligence are enhancing biosensor performance. Integrating biosensor-based diagnostics with knowledge of sex-specific molecular and hormonal pathways may lead to more precise and equitable approaches in CRC detection, selection of therapeutic regimes and management. Full article
(This article belongs to the Special Issue Application of Biosensors in Pharmaceutical Research)
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38 pages, 2034 KB  
Review
The Application of Nanomaterials in Breast Cancer
by Kexin Guo, Yue Sun and Huihua Xiong
Pharmaceutics 2025, 17(12), 1608; https://doi.org/10.3390/pharmaceutics17121608 - 14 Dec 2025
Viewed by 662
Abstract
Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) [...] Read more.
Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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35 pages, 968 KB  
Review
Advancing Lung Cancer Treatment: A Comprehensive Review of Photodynamic Therapy and Nanoparticle Applications
by Andreea Moise-Crintea, Anne-Marie Constantin, Elena Mihaela Jianu, Ioana Maria Orlea, Minodora Manea, Roxana Oana Cojocariu, Rahela Carpa, Bogdan-Andrei Borlea, Cristina-Maria Boznea, Razvan Lucian Coseriu and Alina Sovrea
Pharmaceutics 2025, 17(12), 1579; https://doi.org/10.3390/pharmaceutics17121579 - 8 Dec 2025
Viewed by 1120
Abstract
Lung cancer remains a significant global health challenge. The high mortality rate is primarily caused by late diagnoses and the limitations of conventional therapies. Photodynamic therapy (PDT), which uses photosensitizing compounds, specific wavelengths of light, and oxygen to generate cytotoxic reactive oxygen species [...] Read more.
Lung cancer remains a significant global health challenge. The high mortality rate is primarily caused by late diagnoses and the limitations of conventional therapies. Photodynamic therapy (PDT), which uses photosensitizing compounds, specific wavelengths of light, and oxygen to generate cytotoxic reactive oxygen species (ROS) that selectively destroy cancer cells, has emerged as a promising, minimally invasive alternative. Despite its advantages, traditional PDT has limitations. These include the limited penetration depth of light and the hypoxic nature of the tumor microenvironment. Nanotechnology has transformed PDT by enabling the precise delivery of photosensitizers, improving their stability, overcoming physiological barriers, and allowing for deeper tissue targeting. This review analyzes the molecular mechanisms of PDT, the evolution of photosensitizer and nanoparticle design, strategies to overcome PDT limitations, and the impact of the tumor microenvironment. Additionally, the potential of combining PDT with other cancer therapies, such as chemotherapy, immunotherapy, targeted therapy, radiotherapy, and gene therapy, is being investigated. While preclinical successes are remarkable, clinical implementation of nanoparticle-based PDT faces complex regulatory pathways, manufacturing scalability challenges, and the need for robust long-term safety data. Integrating artificial intelligence (AI) and biomarker discovery will accelerate the development of personalized treatments and usher in a new era of targeted oncology for lung cancer patients. Full article
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28 pages, 1093 KB  
Review
Targeting Ferroptosis in Nasopharyngeal Carcinoma: Mechanisms, Resistance, and Precision Therapeutic Opportunities
by Jaewang Lee and Jong-Lyel Roh
Int. J. Mol. Sci. 2025, 26(23), 11439; https://doi.org/10.3390/ijms262311439 - 26 Nov 2025
Viewed by 1177
Abstract
Nasopharyngeal carcinoma (NPC) is a head and neck malignancy strongly associated with Epstein–Barr virus (EBV) infection and characterized by high radiosensitivity but frequent therapy resistance. Despite advances in radiotherapy, chemotherapy, and immunotherapy, relapse and metastasis remain major challenges, underscoring the need for novel [...] Read more.
Nasopharyngeal carcinoma (NPC) is a head and neck malignancy strongly associated with Epstein–Barr virus (EBV) infection and characterized by high radiosensitivity but frequent therapy resistance. Despite advances in radiotherapy, chemotherapy, and immunotherapy, relapse and metastasis remain major challenges, underscoring the need for novel therapeutic approaches. This review aims to provide an integrated overview of the molecular mechanisms governing ferroptosis in NPC and to clarify how these pathways contribute to therapy resistance while revealing potential therapeutic vulnerabilities. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising target in NPC. Core regulators include the system xCT–GSH–GPX4 antioxidant axis, iron metabolism, and lipid remodeling enzymes such as ACSL4, with epigenetic modifiers (METTL3, IGF2BP2, HOXA9) and EBV-driven signaling further shaping ferroptosis responses. EBV-driven oncogenic programs substantially reshape ferroptosis sensitivity in NPC by activating the Nrf2/Keap1 antioxidant axis, stabilizing SLC7A11 and GPX4, and modulating iron and redox metabolism. These viral mechanisms suppress ferroptotic stress and contribute to both radioresistance and chemoresistance. Suppression of ferroptosis underlies both radioresistance and chemoresistance, whereas restoration of ferroptosis re-sensitizes tumors to treatment. Natural compounds including solasodine, berberine, cucurbitacin B, and celastrol-curcumin combinations, as well as pharmacologic modulators such as HO-1 inhibitors and GPX4 antagonists, have shown ferroptosis-inducing effects in preclinical models, although their translational potential remains to be clarified. Nanotechnology-based platforms (e.g., Bi2Se3 nanosheet hydrogels) further enhance efficacy and reduce toxicity by enabling controlled drug delivery. Biomarker discovery, encompassing ferroptosis-related gene signatures, epigenetic regulators, immune infiltration patterns, EBV DNA load, and on-treatment redox metabolites, provides a foundation for patient stratification. Integration of ferroptosis modulation with radiotherapy, chemotherapy, and immunotherapy represents a compelling strategy to overcome therapy resistance. In synthesizing these findings, this review highlights both the mechanistic basis and the translational promise of ferroptosis modulation as a strategy to overcome treatment resistance in NPC. Future directions include biomarker validation, optimization of drug delivery, early-phase clinical trial development, and multidisciplinary collaboration to balance ferroptosis induction in tumors while protecting normal tissues. Collectively, ferroptosis is emerging as both a vulnerability and a therapeutic opportunity for improving outcomes in NPC. Full article
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33 pages, 1158 KB  
Review
Converging Structural Biology and Nanotechnology to Decipher and Target Alzheimer’s Disease: From Atomic Insights to Clinical Translation
by Akshata Yashwant Patne, Imtiyaz Bagban and Meghraj Vivekanand Suryawanshi
BioChem 2025, 5(4), 40; https://doi.org/10.3390/biochem5040040 - 18 Nov 2025
Viewed by 935
Abstract
Alzheimer’s disease (AD), the leading cause of dementia, is defined by two pathological hallmarks, amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—both now structurally resolved at near-atomic precision thanks to cryo-EM. Despite decades of research, effective disease-modifying therapies remain elusive, underscoring the need for [...] Read more.
Alzheimer’s disease (AD), the leading cause of dementia, is defined by two pathological hallmarks, amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—both now structurally resolved at near-atomic precision thanks to cryo-EM. Despite decades of research, effective disease-modifying therapies remain elusive, underscoring the need for innovative interdisciplinary approaches. This review synthesizes recent advances in structural biology and nanotechnology, highlighting their synergistic potential in revolutionizing AD diagnosis and treatment. Cryo-EM and NMR have revolutionized our understanding of Aβ/tau polymorphs, revealing structural vulnerabilities ripe for therapeutic targeting—yet clinical translation remains bottlenecked by the blood–brain barrier (BBB). Concurrently, nanotechnology offers groundbreaking tools, including nanoparticle-based drug delivery systems for blood–brain barrier (BBB) penetration, quantum dot biosensors for early Aβ detection, and CRISPR-nano platforms for APOE4 gene editing. We discuss how integrating these disciplines addresses critical challenges in AD management—from early biomarker detection to precision therapeutics—and outline future directions for translating these innovations into clinical practice. Full article
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24 pages, 4520 KB  
Review
Radiolabeled LHRH and FSH Analogues as Cancer Theranostic Agents: A Systematic Review
by Anna Giorgio, Michela Varani, Chiara Lauri, Valeria Bentivoglio and Pallavi Nayak
J. Clin. Med. 2025, 14(21), 7811; https://doi.org/10.3390/jcm14217811 - 3 Nov 2025
Cited by 1 | Viewed by 775
Abstract
Background: G-protein-coupled receptors (GPCRs) play pivotal roles in tumor growth and progression. Among these, the luteinizing hormone-releasing hormone receptor (LHRH-R) and follicle-stimulating hormone receptor (FSH-R) represent promising translational targets, unlike luteinizing hormone receptors (LH-Rs). Indeed, both LHRH-R and FSH-R are selectively expressed in [...] Read more.
Background: G-protein-coupled receptors (GPCRs) play pivotal roles in tumor growth and progression. Among these, the luteinizing hormone-releasing hormone receptor (LHRH-R) and follicle-stimulating hormone receptor (FSH-R) represent promising translational targets, unlike luteinizing hormone receptors (LH-Rs). Indeed, both LHRH-R and FSH-R are selectively expressed in various cancers and their vasculature, offering opportunities for receptor-mediated imaging and therapy. Objectives: This systematic review aims to evaluate radiolabeled LHRH- and FSH-derivative biomolecules, including peptides, monoclonal antibodies and nanocarriers, for their applications in cancer diagnosis and treatment. Methods: The systematic review was conducted following PRISMA 2020 guidelines. A systematic search of PubMed, Scopus and Web of Science was conducted for studies published between 2005 and 2025. A total of 248 records were identified, and 156 articles were screened after removing duplicate records. Two authors independently selected eligible studies. Quality of evidence was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) approach. Results: A total of 25 studies met the inclusion criteria and were included in the final review. Radiolabeled LHRH and FSH derivatives showed receptor-specific tumor localization in both preclinical and clinical applications. FSH-R expression in tumor blood vessels supports its potential as a biomarker for early cancer diagnosis. FSHβ-derived peptides exhibit improved pharmacokinetics compared to monoclonal antibodies in PET imaging. LHRH analogues, particularly D-Lys6-modified peptides, proved effective for SPECT, PET and therapeutic applications, particularly in breast and prostate cancer. The integration of radiolabeled LHRH and FSH derivatives with nanocarriers further enhanced probe stability and tumor targeting, increasing tumor accumulation and image contrast compared to free peptide. Conclusions: Radiopharmaceuticals targeting LHRH-R and FSH-R are promising tools for cancer imaging and treatment. Advances in nanotechnology enhance delivery precision and reduce systemic toxicity, thereby increasing its translational promise in oncology. Full article
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27 pages, 7879 KB  
Article
Melittin Nanoparticles Mitigate Glyphosate-Induced Nephrotoxicity via Cytokine Modulation and Bax/Nrf2 Pathways
by Amany M. Hamed, Zeyad Elsayed Eldeeb Mohana, Azza M. A. Abouelella, Wafaa A. Abdellah, Dalia A. Elbahy, Noha A. R. Fouda, Dina M. Monir, Safaa S. Soliman, Ahmed Mohamed Mahmoud Abdelfattah Elkassas, Elsayed Eldeeb Mehana Hamouda, Hany M. R. Abdel-Latif, Ahmed R. H. Ahmed and Nadia S. Mahrous
Biomedicines 2025, 13(11), 2607; https://doi.org/10.3390/biomedicines13112607 - 24 Oct 2025
Viewed by 1963
Abstract
Background/Objectives: Glyphosate-based herbicides (GBHs) are widely used agrochemicals implicated in nephrotoxicity through mechanisms involving oxidative stress, inflammation, and tissue remodeling. Natural peptides such as melittin possess potent anti-inflammatory and antioxidant properties; however, their therapeutic use is limited by instability and toxicity. Nanotechnology-based encapsulation [...] Read more.
Background/Objectives: Glyphosate-based herbicides (GBHs) are widely used agrochemicals implicated in nephrotoxicity through mechanisms involving oxidative stress, inflammation, and tissue remodeling. Natural peptides such as melittin possess potent anti-inflammatory and antioxidant properties; however, their therapeutic use is limited by instability and toxicity. Nanotechnology-based encapsulation presents a promising approach to overcoming these challenges. Objective: This study aimed to evaluate the protective effects of melittin-loaded chitosan–TPP nanoparticles (MEL-NPs) against glyphosate-induced nephrotoxicity in rats, with emphasis on oxidative, inflammatory, and apoptotic pathways. Methods: Female Wistar rats were divided into four groups: control, glyphosate (5 mg/kg/day, 25 days), glyphosate + free melittin, and glyphosate + MEL-NPs (40 µg/kg, orally, 3 times/week). Renal function biomarkers, oxidative stress parameters (MDA, GSH, SOD, CAT, NO), cytokines (TNF-α, IL-6), and serum protein/iron indices were assessed. Western blotting (Nrf2, NGAL), histopathology (H&E), and immunohistochemistry (Bax) were performed. Nanoparticles were characterized by TEM, FTIR, and UV–Vis spectroscopy. Results: Glyphosate exposure caused renal dysfunction, including elevated plasma urea and creatinine levels, and reduced creatinine clearance, indicating impaired glomerular filtration efficiency, oxidative stress (↑increased MDA, NO; ↓decreased GSH, SOD), and upregulation of pro-inflammatory cytokines. Histology revealed tubular degeneration and inflammatory infiltration, while NGAL and Bax were strongly induced. Nrf2 expression was elevated as a compensatory response. Free melittin partially ameliorated these alterations, whereas MEL-NPs provided superior protection, restoring renal function, normalizing oxidative balance, reducing NGAL and Bax expression, and preserving renal histoarchitecture. Conclusions: Melittin nanoparticles confer robust renoprotection against glyphosate-induced nephrotoxicity in rats by modulating oxidative stress, suppressing inflammation, and regulating Nrf2/Bax signaling. These findings highlight nano-melittin as a promising therapeutic platform for managing herbicide-related renal disorders. Full article
(This article belongs to the Section Cell Biology and Pathology)
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