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Search Results (239)

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Keywords = precision nanomedicine

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31 pages, 4531 KB  
Review
Enzymatic Nanomotors Integrated with Plant Extracts: Biochemical Mechanisms, Applications, and Clinical Perspectives
by Joanna Lemanowicz, Kinga Gawlińska, Iwona Jaskulska, Emilia Leśniak and Antoni Kuczyński
Molecules 2026, 31(13), 2344; https://doi.org/10.3390/molecules31132344 - 3 Jul 2026
Viewed by 212
Abstract
Enzymatic nanomotors (EMNMs) represent an emerging class of intelligent nanosystems that exploit enzymatic biocatalysis to generate autonomous motion within biological environments, including complex cellular and tissue contexts within living organisms. Owing to their ability to utilize endogenous biofuels, high biocompatibility, and capacity for [...] Read more.
Enzymatic nanomotors (EMNMs) represent an emerging class of intelligent nanosystems that exploit enzymatic biocatalysis to generate autonomous motion within biological environments, including complex cellular and tissue contexts within living organisms. Owing to their ability to utilize endogenous biofuels, high biocompatibility, and capacity for targeted propulsion, EMNMs have demonstrated considerable potential in diverse biomedical applications. These include targeted drug delivery, cancer therapy, diagnostics, and bioimaging, as well as the traversal of biological barriers. This review comprehensively discusses the mechanisms underlying enzyme-driven propulsion, nanomotor design strategies, and their current and prospective applications in medicine, while also addressing major challenges associated with enzymatic stability, biocompatibility, motion control, and clinical safety. Furthermore, future perspectives are highlighted, including enzyme cascade systems, intelligent nanomotor swarms, biodegradable materials, and strategies facilitating clinical translation. As a representative example of practical application, curcumin was employed as a model therapeutic agent due to its well-established anticancer, anti-inflammatory, and antioxidant properties, enabling evaluation of the nanomotors’ capability for controlled, pH-responsive release of therapeutic cargo. Nanophytomedicine enhances the therapeutic efficacy of phytochemicals by improving their stability, bioavailability, and targeted delivery through nanocarrier systems. The integration of phytotherapy with nanotechnology offers promising opportunities for the development of safer and more effective therapeutic strategies. Full article
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36 pages, 4265 KB  
Review
Nanoparticle-Based Biomaterials in Cancer Research: From Mechanistic Insights to Therapeutic Innovation
by Manoochehr Rasekh and Sassan Hafizi
Int. J. Mol. Sci. 2026, 27(13), 5930; https://doi.org/10.3390/ijms27135930 - 1 Jul 2026
Viewed by 273
Abstract
Cancer remains one of the most complex diseases to study and treat, with tumour microenvironment heterogeneity and therapeutic resistance continuing to limit clinical progress. Biomaterials-based nanoparticles have emerged as versatile platforms that not only advance understanding of cancer biology but also enable innovative [...] Read more.
Cancer remains one of the most complex diseases to study and treat, with tumour microenvironment heterogeneity and therapeutic resistance continuing to limit clinical progress. Biomaterials-based nanoparticles have emerged as versatile platforms that not only advance understanding of cancer biology but also enable innovative therapeutic strategies. As mechanistic tools, nanoparticles can be used to investigate extracellular matrix interactions, mechanotransduction pathways, drug resistance, and tumour–immune crosstalk, providing insights into how physical and biochemical cues influence disease progression. Therapeutically, engineered nanoparticle systems have been developed for the targeted delivery of chemotherapeutics, nucleic acids, and immunomodulatory agents, incorporating features such as stimuli-responsive release, multifunctionality, and theranostic capabilities. Recent advances in patient-derived tumour models, high-throughput screening platforms, and artificial intelligence-assisted design are further driving the development of precision nanomedicine. Despite ongoing challenges related to biodistribution, safety, manufacturing scalability, and regulatory approval, nanoparticle-based biomaterials offer significant opportunities to bridge fundamental cancer research and clinical translation. This review highlights recent mechanistic and therapeutic advances, discusses key translational barriers, and outlines future directions at the interface of biomaterials, nanotechnology, and oncology. Full article
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34 pages, 1202 KB  
Review
Biogenic Metal Nanoparticles from Indian Flora as Programmable Bio-Interfaces: From Phytochemical Coronas to Precision Nanomedicine
by Sharad Shriram Tat, Kailas D. Datkhile, Jayant R. Pawar, Amar R. Mohite and Tanisha Sharma
Int. J. Mol. Sci. 2026, 27(13), 5837; https://doi.org/10.3390/ijms27135837 - 28 Jun 2026
Viewed by 371
Abstract
Biogenic metal nanoparticles are naturally covered with the phytochemical corona, which includes plant-derived metabolites. Emerging evidence suggests that the phytochemical corona, together with the intrinsic properties of the metallic core, contributes significantly to the biological identity, therapeutic behavior, and safety profile of biogenic [...] Read more.
Biogenic metal nanoparticles are naturally covered with the phytochemical corona, which includes plant-derived metabolites. Emerging evidence suggests that the phytochemical corona, together with the intrinsic properties of the metallic core, contributes significantly to the biological identity, therapeutic behavior, and safety profile of biogenic nanoparticles. In this review, we go beyond the traditional view of plant extracts as reducing and capping agents to the phytochemical corona as a programmable nano–bio interface. Green synthesis from Indian flora has potential that can yield coronas rich in flavonoids, polyphenols, terpenoids, and alkaloids. Each corona composition contributes to different physicochemical properties, such as cellular interactions and downstream effects on reactive oxygen species, endocytic uptake and signaling pathways (p53, AKT, MAPK). When in contact with biological fluids, the corona adsorbs host proteins, giving rise to a hybrid interface that further influences the therapeutic outcome. The corona composition directly contributes to the biological activities of these nanoparticles: for example, anticancer, antimicrobial, antioxidant, and antiparasitic. The corona offers intrinsic targeting, stimuli-responsive release and improved stability for drug delivery. Toxicity and safety assessment shows dose-dependent effects, organ accumulation and long-term concerns for which standardized testing is needed. Translational challenges include: reproducibility, seasonal and geographic phytochemical variation, variability in extraction methods, scalability, shelf life and regulatory ambiguity. Future directions include Artificial intelligence (AI)-driven phytosynthesis, precision nanomedicine, nano–bio interface engineering, multi-omics integration, exploration of endangered Indian flora, and digital twin modeling. This review provides a roadmap for engineering phytochemical coronas as precision nanomedicine platforms by shifting the focus from core to corona and from empirical recipes to predictive design. It positions biogenic nanoparticles not only as eco-friendly alternatives, but as programmable, superior therapeutics for cancer and drug-resistant infections. Full article
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21 pages, 2051 KB  
Review
Extracellular Vesicles, Liposomes, and Hybrid Nanovesicles: Comparative Strategies for Targeted Cancer Therapy
by Alessia Brossa, Michela Arena, Elena Ceccotti, Enza Di Gregorio, Giuseppe Ferrauto, Benedetta Bussolati and Stefania Bruno
Int. J. Mol. Sci. 2026, 27(13), 5795; https://doi.org/10.3390/ijms27135795 - 26 Jun 2026
Viewed by 152
Abstract
Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; [...] Read more.
Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; however, their performance is limited by tumor heterogeneity, vascular barriers, adverse effects and inefficient intracellular drug release. EVs are naturally derived nanoparticles involved in intercellular communication and exhibit intrinsic biocompatibility, low immunogenicity, and biological targeting potential; yet their translation is constrained by heterogeneity, limited loading capacity, and manufacturing challenges. Different studies indicate complementary advantages between both systems, with EVs favoring biological targeting and immune modulation and liposomes enabling controlled formulation and pharmacokinetic optimization. These features have driven the development of hybrid EV–liposome nanovesicles, which integrate synthetic and biological properties to enhance tumor targeting, therapeutic efficacy, and payload diversity, including drugs, nucleic acids, and gene-editing systems. Despite promising preclinical results, challenges remain in scalability, standardization, and mechanistic understanding of in vivo behaviour. Overall, these hybrid strategies represent a promising platform for next-generation precision nanomedicine in cancer therapy and for advancing clinical translation by addressing key limitations of current delivery systems and improving therapeutic index and patient outcomes. Full article
(This article belongs to the Special Issue RNA in Human Diseases: Challenges and Opportunities: 2nd Edition)
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47 pages, 2613 KB  
Review
Artificial Intelligence in Nanopharmaceutical Development: From Predictive Design to Clinical Translation
by Renato Sonchini Gonçalves
Pharmaceutics 2026, 18(6), 764; https://doi.org/10.3390/pharmaceutics18060764 - 22 Jun 2026
Viewed by 405
Abstract
Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic [...] Read more.
Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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21 pages, 618 KB  
Review
Nanomedicine in Cardiovascular Inflammation: Novel Diagnostic and Therapeutic Strategies
by Aikaterini-Eleftheria Karanikola, Agapi Ploussi, Dimitrios Tsiachris and Efstathios P. Efstathopoulos
J. Pers. Med. 2026, 16(6), 328; https://doi.org/10.3390/jpm16060328 - 18 Jun 2026
Viewed by 369
Abstract
Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a [...] Read more.
Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a promising yet underexplored approach to address these challenges by enabling precise molecular imaging and site-specific therapeutic interventions. This review summarizes current and emerging nanotechnology-based approaches for the diagnosis and treatment of cardiovascular inflammation, highlighting their potential in clinical practice and remaining challenges. In addition, recent advances, including the development of biomimetic nanoplatforms, are discussed, along with future perspectives and the potential integration of artificial intelligence to further enhance precision in cardiovascular medicine. Full article
(This article belongs to the Special Issue Personalized Prevention and Treatment of Cardiovascular Diseases)
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30 pages, 4306 KB  
Review
Physicochemical Aspects of Mixed Micelle Formation Between Amphiphilic Drugs and Surfactants
by Ádám Juhász, Bianka Torma, Egon F. Várkonyi, László Seres, Norbert Varga, Árpád Turcsányi and Edit Csapó
Int. J. Mol. Sci. 2026, 27(12), 5400; https://doi.org/10.3390/ijms27125400 - 15 Jun 2026
Viewed by 244
Abstract
The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs [...] Read more.
The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs and surfactants into synergistic nanostructures. By articulating the transition from traditional guest/host solubilization to “drug-as-component” models, we highlight the critical role of molecular interactions in achieving therapeutic precision. It further outlines the experimental methodologies used to investigate these systems and elucidates how they enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Special emphasis is placed on the practical applications of synergy in reducing systemic toxicity and optimizing drug release kinetics, providing a roadmap for the development of next-generation nano-pharmaceuticals. The functionality of these systems is significantly influenced by the molecular interactions among their constituents; thus, quantitative analysis of these interactions might enhance the formulation of more effective pharmaceuticals. This review outlines the key physicochemical principles of mixed micelle formation, including thermodynamics and synergistic interactions of amphiphiles, while emphasizing their relevance in current research and practical pharmaceutical applications. Various experimental methods, such as surface tension measurement, conductometric and calorimetric tests, and spectroscopic techniques, are compared in terms of their conditions of application and performance in understanding micelle formation and micelle structure. We clearly point out that the interpretation and evaluation of the properties of colloidal systems containing drug molecules solubilized by mixed micelles and an amphiphilic drug incorporated into micelles must be discussed and evaluated separately. Understanding the limitations and characteristics of the physical/chemical principles applied is essential for the rational design of mixed micelle carriers tailored to specific therapeutic needs. Full article
(This article belongs to the Special Issue Nanotechnology in Drug Delivery: Applications and Perspectives)
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26 pages, 2485 KB  
Review
Advances in Nano-Drug Delivery Systems for Chronic Autoimmune Diseases: A Focus on Diabetes Mellitus, Inflammatory Bowel Disease, and Rheumatoid Arthritis
by Mengqing Hu, Yimiao Zhou, Lin Yang, Liquan Zhou, Xiao Liu, Tianjin Ma and Zuowei Xiao
Molecules 2026, 31(12), 2094; https://doi.org/10.3390/molecules31122094 - 14 Jun 2026
Viewed by 508
Abstract
The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. [...] Read more.
The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article
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26 pages, 2151 KB  
Systematic Review
Microfluidics for Drug Encapsulation and Controlled Release: A Systematic Review of Recent Advances
by Leonardo D. Binda, Mario A. Cachile, María V. D’Angelo and María C. Martínez Ceron
J. Pharm. BioTech Ind. 2026, 3(2), 13; https://doi.org/10.3390/jpbi3020013 - 10 Jun 2026
Viewed by 258
Abstract
Background: Conventional drug delivery systems often lead to fluctuating plasma concentrations (“Peak and Trough” phenomenon), causing toxicity or inefficacy. Microfluidics has emerged as a revolutionary tool to overcome, among other applications, the limitations of conventional bulk encapsulation methods, such as polydispersity and poor [...] Read more.
Background: Conventional drug delivery systems often lead to fluctuating plasma concentrations (“Peak and Trough” phenomenon), causing toxicity or inefficacy. Microfluidics has emerged as a revolutionary tool to overcome, among other applications, the limitations of conventional bulk encapsulation methods, such as polydispersity and poor reproducibility. Methods: A systematic review of the literature published between 2020 and 2025 was conducted to evaluate the application of microfluidics in the synthesis of advanced nanomedicines. The review focused on Lipid Nanoparticles (LNPs), Polymeric Nanoparticles (PNPs), and Hydrogel Microspheres. Results: Microfluidics enables the production of monodisperse particles with precise control over geometry and drug loading stoichiometry. Key therapeutic applications include oncology (passive and active targeting), gene therapy (mRNA vaccines), and regenerative medicine (diabetic wound healing). Conclusions: While microfluidics offers superior quality control compared to bulk methods, industrial scalability remains the primary challenge, currently addressed through parallelization and continuous flow strategies. Full article
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40 pages, 20067 KB  
Review
Advances in Nanomedicine for Modulating DNA Methylation and Inducing Pyroptosis
by Shibo Wang, Xincong Li, Hao Liu, Jiali Zhang, Jiaxi Li, Xu Jin and Chenjie Fang
J. Nanotheranostics 2026, 7(2), 14; https://doi.org/10.3390/jnt7020014 - 5 Jun 2026
Viewed by 241
Abstract
DNA methylation is a key mechanism in epigenetic regulation and plays a pivotal role in tumor initiation, progression, and therapeutic resistance. We begin by elucidating how the dysregulation of key DNA methylation enzymes in tumors drives concurrent global hypomethylation and cytosine-phosphate-guanine (CpG) island [...] Read more.
DNA methylation is a key mechanism in epigenetic regulation and plays a pivotal role in tumor initiation, progression, and therapeutic resistance. We begin by elucidating how the dysregulation of key DNA methylation enzymes in tumors drives concurrent global hypomethylation and cytosine-phosphate-guanine (CpG) island hypermethylation. This aberrant epigenetic landscape promotes tumorigenesis through silencing tumor suppressor genes and triggering abnormal activation of oncogenic signaling pathways. Notably, DNA methylation is intimately linked to cellular pyroptosis. In particular, the hypermethylation-mediated silencing of pyroptosis effector genes represents a critical epigenetic mechanism underlying acquired drug resistance. Targeting DNA methylation with epigenetic drugs offers a novel strategy to resensitize tumors to chemotherapy, radiotherapy, and immunotherapy. Moreover, advances in nanomedicine have yielded smart platforms for the precise administration of epigenetic modulators and combination therapies. These platforms enable a coordinated “epigenetic priming-pyroptosis execution” strategy, which holds promises for reversing therapeutic resistance and remodeling the tumor immune microenvironment. By integrating DNA methylation regulation, pyroptosis mechanisms, and nano-targeted strategies, this review aims to provide a theoretical framework and novel perspectives for developing innovative, epigenetically driven anti-tumor therapies. Full article
(This article belongs to the Special Issue Feature Review Papers in Nanotheranostics)
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36 pages, 3189 KB  
Review
Revisiting the Lipid–Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology
by Dimitris C. Kounatidis, Natalia G. Vallianou, Fotis Panagopoulos, Antonios Bampiolakis, Vasileios Stamatopoulos, Maria Dalamaga, Iordanis Mourouzis and Constantinos Pantos
Biomolecules 2026, 16(6), 831; https://doi.org/10.3390/biom16060831 - 4 Jun 2026
Viewed by 559
Abstract
Cancer remains a major global health challenge, with persistent limitations in early diagnosis, metastatic disease control, and the achievement of durable therapeutic responses with acceptable toxicity. These challenges highlight the need for more precise biomarkers and more effective therapeutic strategies. Increasing evidence implicates [...] Read more.
Cancer remains a major global health challenge, with persistent limitations in early diagnosis, metastatic disease control, and the achievement of durable therapeutic responses with acceptable toxicity. These challenges highlight the need for more precise biomarkers and more effective therapeutic strategies. Increasing evidence implicates dysregulated lipid metabolism as a central contributor to tumor development and progression. In recent years, proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), and cholesteryl ester transfer protein (CETP) have gained particular attention due to their roles in cholesterol homeostasis, oncogenic signaling, and immune modulation within the tumor microenvironment (TME). This narrative review evaluates the potential of these lipid-regulatory mediators as diagnostic biomarkers and therapeutic targets in oncology. The majority of available evidence derives from preclinical and epidemiological studies, with PCSK9 representing the most extensively investigated target. Findings are sometimes contradictory and strongly influenced by tumor type, disease stage, and biological context, which currently precludes the clinical applicability of these molecules as reliable biomarkers. Similar limitations apply to their translational potential as actionable therapeutic targets. Nevertheless, emerging preclinical evidence suggests that modulation of these glycoproteins may enhance the efficacy of chemotherapy, targeted therapies, and immunotherapy, including nanomedicine-based approaches. Of note, clinical research investigating the role of PCSK9 inhibition in oncology is currently ongoing, whereas comparable studies focusing on ANGPTL3 and CETP remain scarce. Overall, further mechanistic, translational, and prospective clinical investigations are warranted to elucidate the involvement of these lipid-regulatory proteins in cancer biology and to define their potential integration into future oncologic diagnostic and therapeutic strategies. Full article
(This article belongs to the Section Lipids)
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24 pages, 1249 KB  
Article
Elucidating the Influence of Serum Concentration, Sex, and Particle Size on Iron Oxide Nanoparticle–Lipid Biocorona Formation
by Jenna N. Swihart, Christina R. Ferreira, Akshada Shinde and Jonathan H. Shannahan
Nanomaterials 2026, 16(11), 683; https://doi.org/10.3390/nano16110683 - 1 Jun 2026
Viewed by 495
Abstract
Biocorona (BC) formation is a critical determinant of nanoparticle (NP) biological identity and downstream interactions, yet lipid association within BCs remains comparatively understudied relative to proteins, despite its potential relevance to NP stability, biodistribution, cellular interactions, and clearance. A more complete understanding of [...] Read more.
Biocorona (BC) formation is a critical determinant of nanoparticle (NP) biological identity and downstream interactions, yet lipid association within BCs remains comparatively understudied relative to proteins, despite its potential relevance to NP stability, biodistribution, cellular interactions, and clearance. A more complete understanding of NP–lipid interactions is essential for optimizing NP-based therapies and supporting their safe clinical translation. In this study, we evaluated how serum concentration, biological sex, and NP size influence lipid association with iron oxide (Fe3O4) NP BCs. Lipids associated with 50 or 100 nm Fe3O4 NPs were characterized following incubation in male or female human serum across increasing serum concentrations of 5%, 10%, 25%, 50%, or 75% (v/v). Increasing serum concentration promoted greater lipid association and increased BC complexity, with higher serum conditions yielding more compositionally diverse lipid coronas. BCs formed on 50 nm Fe3O4 NPs consistently contained more lipid species than those formed on 100 nm Fe3O4 NPs, indicating pronounced size-dependent differences in lipid recruitment. BCs formed in male serum also contained more lipid species and a greater number of unique lipids than corresponding female BCs, demonstrating that biological sex significantly influenced both lipid composition and abundance within the BC. Rank-based comparisons further indicated that lipid association was governed not only by serum abundance but also by selective binding behaviors. Together, these findings demonstrate that lipid corona formation is strongly shaped by both the biofluid environment and NP design variables, emphasizing the importance of considering lipid coronas in NP design and evaluation, particularly for applications in drug delivery, nanomedicine, and precision diagnostics. Full article
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34 pages, 4482 KB  
Review
Microfluidic-Driven Assembly of RNA Nanocomplexes: Design, Process Control and Translational Perspectives in Oncology
by Ronan Pinto Nobrega dos Santos, Dana Celeste Betancourt Roldan, Muslum Guven, Lucas Campana Leite, Francisco Jacomine Madrid Furlan, Gabriel Rocha Mariano da Silva, Vitória Almeida Pessoa de Oliveira, Carolline da Silva Capriglione, Josie Pereira da Silva, José Carlos Pinto, Ismail Eş and Tiago Albertini Balbino
Pharmaceutics 2026, 18(6), 679; https://doi.org/10.3390/pharmaceutics18060679 - 29 May 2026
Viewed by 893
Abstract
RNA-based therapeutics are becoming increasingly important in oncology, particularly following the rapid development of mRNA technologies during the COVID-19 pandemic, but their success strongly depends on how efficiently they can be delivered to target cells. Microfluidic technologies have redefined the design and manufacturing [...] Read more.
RNA-based therapeutics are becoming increasingly important in oncology, particularly following the rapid development of mRNA technologies during the COVID-19 pandemic, but their success strongly depends on how efficiently they can be delivered to target cells. Microfluidic technologies have redefined the design and manufacturing of RNA-based nanocomplexes, as they enable precise control over physicochemical features that are critical for clinical translation in oncology. This review examines recent developments in microfluidic-assisted synthesis of RNA nanocarriers, with a focus on cancer applications. Through a detailed analysis of material systems, device architectures, and formulation strategies, we explore how laminar flow environments enable reproducible encapsulation, tunable particle size, and improved payload stability. We examine the microfluidic assembly of lipid nanoparticles and polymeric carriers for RNA delivery, highlighting strategies to enhance durability, bioavailability, and cellular uptake. Advancements in process optimization, including flow parameter refinement and inline monitoring, are discussed alongside the influence of device geometries on mixing dynamics and nucleation. Beyond formulation, we explore the integration of microfluidics with tumor-on-chip platforms to evaluate transport, penetration, and therapeutic response in physiologically relevant cancer models. By connecting technological innovation with preclinical application, this work outlines the trajectory toward next-generation, personalized RNA nanomedicines enabled by microfluidic precision. Full article
(This article belongs to the Special Issue Microfluidic Assembly of Nanocomplexes for Drug and Gene Delivery)
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26 pages, 5365 KB  
Review
Polymeric Nano Drug Delivery Systems for Overcoming Tumor Microenvironment-Mediated Drug Resistance
by Yonggyu Kang, Jeongeun Kim, Jisu Park, Subin Lee, Youngjin An, Kwang Suk Lim and Hyun-Ouk Kim
Pharmaceutics 2026, 18(6), 674; https://doi.org/10.3390/pharmaceutics18060674 - 29 May 2026
Viewed by 546
Abstract
The tumor microenvironment (TME) acts as a major barrier to effective drug delivery and contributes to drug resistance in solid tumors. Hypoxia, acidosis, and elevated interstitial fluid pressure limit drug penetration, while cancer-associated fibroblasts and immunosuppressive cells promote survival signaling, drug efflux, and [...] Read more.
The tumor microenvironment (TME) acts as a major barrier to effective drug delivery and contributes to drug resistance in solid tumors. Hypoxia, acidosis, and elevated interstitial fluid pressure limit drug penetration, while cancer-associated fibroblasts and immunosuppressive cells promote survival signaling, drug efflux, and metabolic adaptation. Polymeric drug delivery systems offer a promising strategy to address these barriers because their structures can be precisely engineered and designed to respond to TME-specific stimuli. These properties enable controlled drug release at tumor sites and help improve therapeutic efficacy while reducing systemic limitations. This review discusses how physicochemical and cellular components of the TME contribute to drug resistance and how polymeric nanomedicines can be designed to overcome these barriers. In addition, it examines key challenges that limit clinical translation, including tumor heterogeneity, variable enhanced permeability and retention effects, manufacturing scalability, and regulatory requirements. Finally, this review highlights the future direction of polymer nanomedicine and focuses specifically on developing rational material design, enhancing preclinical models, and developing clinically appropriate strategies to combat TME-mediated drug resistance. Full article
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26 pages, 10665 KB  
Article
Self-Assembled Nanoparticles of Licorice Extract Enhance Skin Penetration and Regulate Barrier Proteins via a Dual-Channel Pathway
by Wenjie Ning, Lingyu Hang, Yuye Xue, Wenting Zha, Run Wang, Kailin Xue, Jiantao Ning, Jiankang Zhao, Liqiang Wang and Hailong Yuan
Pharmaceutics 2026, 18(6), 661; https://doi.org/10.3390/pharmaceutics18060661 - 27 May 2026
Viewed by 371
Abstract
Objective: Self-assembled nanoparticles (SANs) naturally occurring in Traditional Chinese Medicine (TCM) decoctions are promising drug carriers due to their biocompatibility, but uncontrolled assembly often leads to poor stability, limiting transdermal permeability and industrial application. This study aimed to fabricate stable and uniform SANs [...] Read more.
Objective: Self-assembled nanoparticles (SANs) naturally occurring in Traditional Chinese Medicine (TCM) decoctions are promising drug carriers due to their biocompatibility, but uncontrolled assembly often leads to poor stability, limiting transdermal permeability and industrial application. This study aimed to fabricate stable and uniform SANs from licorice by precisely regulating the controlled nanoprecipitation of its water- and alcohol-extracted components. The transdermal delivery efficiency and therapeutic efficacy of the SANs in the treatment of atopic dermatitis (AD) were evaluated. Methods: Licorice self-assembled nanoparticles (LD-SANs) were prepared by mixing water and ethanol extracts of licorice, followed by ethanol evaporation under reduced pressure to trigger nanoprecipitation. In vitro transdermal tests compared the delivery efficiency of six major bioactive compounds between LD-SANs and traditional licorice decoction (LD). The penetration mechanism was investigated via passive diffusion and cellular uptake studies. In an AD mouse model, the therapeutic effects and expression of tight junction (TJ) proteins (Occludin and Claudin-1) were assessed. Results: The average particle size of LD-SANs is 200 nm, and it is uniform and stable. LD-SANs significantly enhanced the delivery efficiency of all six bioactive compounds compared to LD. Mechanistic studies revealed a unique “dual-channel” penetration mechanism: the nanoscale size enabled passive diffusion through hair follicles, intercorneocyte lipid gaps, and skin appendages, while perifollicular antigen-presenting cells (APCs) actively recognized and internalized the nanoparticles, creating a cell-mediated active targeting route that collectively boosted skin accumulation. In the AD model, LD-SANs promoted the expression of Occludin and Claudin-1 in the epidermal granular layer, reinforcing intercellular barrier integrity. Conclusions: By combining “efficient penetration” and “barrier repair”, LD-SANs demonstrated notable therapeutic efficacy in AD. This work transforms a traditional decoction into a well-characterized, high-performance nanomedicine and offers a novel strategy for developing TCM-based transdermal delivery systems. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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