Alzheimer's disease (AD) is a progressive neurodegenerative disorder that places an increasing burden on patients, caregivers, and healthcare systems worldwide. Current disease-modifying therapies (DMTs) are limited by high costs, complex administration, and reliance on advanced biomarker infrastructure, highlighting the shortcomings of existing treatment paradigms. These limitations have sparked growing interest in gene- and nucleic acid-based interventions as upstream strategies to modify AD pathogenesis. Among these, small interfering RNA (siRNA) is especially compelling because it can be rationally programmed, directed at multiple molecular pathways, and paired with rapidly evolving delivery technologies. However, the clinical translation of siRNA therapies for AD is still constrained by challenges in brain-targeted delivery, safety, and sustained efficacy. In this review, we summarize current concepts in AD pathology, highlight recent clinical and translational advances, and critically assess emerging brain-targeted siRNA delivery platforms and their key bottlenecks. Within a precision-medicine framework, brain-targeted siRNA offers the possibility of aligning patient selection, molecular targets, and delivery strategies with biomarker-defined AD endotypes. We discuss both the therapeutic promise and the realistic limitations of siRNA-based approaches for AD, outline priorities for future development, and identify key gaps that must be addressed to enable meaningful clinical implementation.
Nanotubes are one-dimensional tubular structures characterized by nanoscale radial dimensions and micrometer-scale axial lengths. Their hollow inner cavity confers a high specific surface area and distinctive physicochemical properties, enabling remarkable potential in drug delivery, disease diagnostics, and tissue engineering. Extensive research into their biocompatibility and degradability establishes a solid foundation for further development and rational design. A synthesis of current data across relevant systems, including carbon nanotubes (CNTs), boron nitride nanotubes (BNNTs), titanium dioxide nanotubes (TiNTs), halloysite nanotubes (HNTs), anodic aluminium oxide nanotubes (AAOs), lipid nanotubes (LNTs), and polymeric nanotubes (PNTs), reveals how structural features and physicochemical properties govern biological responses and functional performance. This integration supports a unified "structure-property-bioresponse-function" framework, offering a conceptual roadmap and general design principles to guide the next generation of nanotube-based biomaterials.
Pain is a pervasive and multifaceted condition that imposes a significant medical and economic burden worldwide. This burden is underscored by the urgent need for transformative, non-addictive opioid alternatives. Nanomedicine offers a promising avenue for addressing the many limitations associated with conventional pain treatments, such as off-target effects, poor bioavailability, and rapid clearance, while enabling advanced therapeutic approaches such as precise spatiotemporal control and robust delivery of biologics. In this review, we explore the convergence of nanomedicine and pain management. We examine current literature on pain and chronic pain physiology and provide collated pharmacological data on current therapeutic approaches as a reference for formulation development. Recent advancements in lipid-based, polymeric, and inorganic nanoscale drug delivery systems (NDDS) for pain are surveyed, along with their progress toward clinical translation. Strategies for enhancing the efficacy of NDDS for pain are discussed, including supramolecular depot localization methods, active and passive targeting, controlled release kinetics, and the incorporation of stimuli-responsive elements for triggered release. We identify knowledge and technical gaps limiting progression beyond sustained-release formulations toward designs exploiting pain-specific biology. Overall, this review provides a comprehensive overview of the state-of-the-art in nanomedicine-based approaches for pain management and provides a roadmap for future innovations.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation and progressive joint destruction. While conventional pharmacotherapies form the cornerstone of RA management, their efficacy is often limited by suboptimal therapeutic outcomes and severe systemic toxicity. In this context, stimuli-responsive nanoplatforms (SR-NPs) have emerged as a promising approach for precision treatment of RA, enabling on-demand drug release triggered by disease-specific endogenous (e.g., pH, ROS, enzymes, GSH, hypoxia) or exogenous (e.g., light, ultrasound, magnetic fields, heat) cues. This review provides a systematic overview of the cutting-edge applications of SR-NPs, categorizing them into endogenous (single- and multi-stimuli), exogenous (single- and multi-stimuli), and hybrid endogenous-exogenous (e.g., ROS/pH/light, GSH/heat) responsive systems. We critically evaluate the design principles, targeting mechanisms, therapeutic payloads, and performance of each category in preclinical RA models. Our analysis reveals that endogenous systems leverage the pathological microenvironment for disease-dependent actuation, exogenous platforms offer tunable spatiotemporal control, while hybrid designs represent an emerging trend toward synergistic and programmable precision. Despite promising advances in enhanced joint retention and effective inflammation suppression, key challenges concerning stimulus heterogeneity, long-term biocompatibility, and clinical translation remain to be addressed. Taken together, this work underscores the evolution of SR-NPs into intelligent and multifaceted therapeutics, thereby providing a potential framework for personalized RA management.
Ultrasound is widely used for diagnostic imaging and therapy. Microbubbles (MB) are effective reflectors of ultrasound and cavitation enhancers, hence their roles in diagnostic and therapeutic ultrasound. MB must be of controlled size, concentration, biocompatible, and stable for biomedical use. Because of low water solubility and high molecular weight, fluorinated gases are generally used to make MB for biomedical applications. Lipids are a viable approach to stabilize MB for use as ultrasound contrast agents. MB of gas can be condensed into nanodroplets or Phase Shift Microbubbles (PSMB). PSMB can remain condensed following vascular administration, but upon application of ultrasound, can reform MB for use as cavitation nuclei. Because of their small size, PSMBs permeate thrombus and tumor microvasculature. Studies have shown effective sonolysis and tumor ablation with PSMB. Lipid-based systems provide robust opportunities for stabilizing MB and PSMB. Improved lipid coating materials are currently in clinical development for novel ultrasound contrast agents. Using the building blocks of lipids and fluorocarbon gases novel platforms are under development for theranostics-a blending of therapy and diagnostics, referring to an integrated medical approach that combines diagnostic imaging and targeted therapy to personalize patient treatment. For example, a theranostic agent might detect a tumor through imaging while simultaneously delivering a therapeutic drug or radiation to the tumor site. This dual functionality enables precise disease characterization, treatment monitoring, and optimized therapeutic outcomes, improving efficacy and reducing side effects. In addition, MB or nanobubbles can be used for oxygen delivery, and these applications will also be reviewed.
Graphene oxide (GO), a chemically versatile and biocompatible derivative of graphene, has emerged as a highly promising material in the field of bone tissue engineering. This review explores the multifaceted role of GO and other functional graphenic materials (FGMs) in supporting bone regeneration by enhancing osteogenesis, angiogenesis, immunomodulation, and biomineralization. We begin by detailing the physiological principles of bone healing, current clinical approaches to bone repair, and the limitations they present. The discussion then progresses through the chemical foundations of GO and its derivatives, emphasizing their unique surface chemistry and tunable reactivity that enable precise functionalization for biomedical applications. Finally, we highlight the potential of FGM-based composites, with integrated biological molecules, polymers, and small organic compounds, to serve as bioactive, bioresorbable scaffolds that support bone growth and integration. By bridging material science with regenerative medicine, this review underscores the importance of GO as a versatile platform for next-generation bone regeneration strategies.
Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive cancers, with a poor prognosis due to late diagnosis and resistance to chemotherapy. Gemcitabine (GEM) monotherapy was the gold standard treatment for PDAC until the early 2010s, when two combinatorial therapies, FOLFIRINOX and GEM combined with Nab-paclitaxel, showed the benefits of the multi-drug approach and became the reference treatments for PDAC. Despite their undisputed efficacy, the overall survival of treated PDAC patients is very low, reaching approximately 12% at 5 years, and the side effects of these therapeutic protocols remain severe and not tolerated by all patients. Recent advances in understanding PDAC biology have led to new therapeutic strategies, including new drug combinations and nanomedicine. This review summarizes background information about past and present PDAC therapeutic regimens with their benefits and the drawbacks including the appearance of treatment resistance and focuses on two potential strategies to counteract the limitations of the actual therapies. First, we highlight the interest of combining disulfiram, a repurposed anti-alcoholism drug, with GEM, based on evidence of synergism between the two molecules. We then emphasize the use of drug delivery nanosystems for their ability to improve drug stability, targeting and to potentially overcome resistance and reduce side effects. Finally, we discuss the combination of multi-drug therapies and nanomedicine through the design of apposite drug delivery nanocarriers capable of encapsulating more than one drug and ensuring sustained release. This all-in-one approach should be promising for more effective therapies of this challenging disease. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.
Precision drug delivery requires carrier systems that combine safety, structural stability, and targeting capability. As self-assembling protein nanocages that lack viral genetic material, virus-like particles (VLPs) offer favorable biocompatibility together with highly programmable architectures. In this review, we summarize the self-assembly mechanisms of VLPs and discuss major functionalization strategies, including bioorthogonal chemistry, non-canonical amino acid incorporation, and biomimetic mineralization. We further examine how these engineering approaches influence VLP performance in cancer immunotherapy, targeted drug delivery, and molecular imaging. Finally, we discuss key barriers to clinical translation, including scalable manufacturing, batch consistency, and pre-existing immunity. We also outline future directions for the development of engineered VLP platforms in nanomedicine.
Recently, nano-scale delivery approaches have been a field of focus to improve the limitations regarding current traditional delivery systems of phytochemicals to treat age-related disorders. Nanotechnology can help to overcome both the large and small-scale barriers associated with traditional drug and vitamin delivery techniques, such as poor biodistribution, instability, and intracellular trafficking, through cell-targeting and other methods. The main forms of nano-drug delivery systems can be classified under lipid-based nanocarrier systems, polymer-based nanocarrier systems, and inorganic carriers. This report focuses on the former two by presenting a comparative review of the advantages and disadvantages of each platform for the oral delivery of phytochemical-encapsulated drugs to treat age-related disorders. Nano-drug delivery systems were found to increase the anti-aging activities of curcumin, fisetin, quercetin, and astaxanthin. A variety of in vivo and in vitro studies show that nano-scale encapsulation methods have the potential to improve the delivery and bioactivity of anti-aging phytochemicals. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
Nanotechnology has brought revolutionary advances in the pharmaceutical field. Among drug delivery systems, nanocarriers, which enhance the solubility, stability and membrane permeability of numerous drugs, have become indispensable. However, nanocarriers not only amplify the therapeutic potential of drugs but can also increase the toxic potential of excipients used in their formulation. For example, commonly used excipients such as polyethylene glycol, cationic polymers (e.g., polyethylenimine), cationic lipids, metal-based materials, and cyclodextrins may exhibit altered, and often enhanced, toxicological profiles when formulated as nanocarriers. This so-called nano-enabled toxicity of pharmaceutical excipients is frequently overlooked, as excipients with a pharmacopoeial monograph are generally considered safe. However, many of these excipients were approved before the widespread use of nanocarriers, and their safety with respect to nano-enabled toxicity has therefore not been systematically evaluated. Regulatory frameworks are still evolving and only partially address these risks. It is therefore the aim of this review to highlight the nano-enabled toxicity of pharmaceutical excipients, propose methods to assess these additional safety risks during early-stage development, and discuss approaches to replace problematic excipients with safer alternatives.
Oxidative stress (OS) serves as a fundamental pathological component in a multitude of chronic diseases, necessitating an all-round theranostic strategy for simultaneous precision intervention and real-time monitoring. Cerium-based nanomaterials (CeNMs), particularly cerium oxide nanoparticles (CeNPs), offer a disruptive theranostic platform on account of their unique Ce3+/Ce4+ redox cycling, intrinsic superoxide dismutase (SOD)- and Catalase (CAT)-mimetic activities, responsiveness to pathological microenvironments (e.g., high ROS and low pH), and inherent or engineerable imaging capabilities (e.g., CT contrast and fluorescence). This review not only systematically probes deep into four "diagnosis-therapy" bridging mechanisms of CeNMs in oxidative-stress-correlated diseases, but also digs into how these mechanisms effectively address the limitations of conventional strategies. On that account, we explore the integrated potential of CeNMs in antioxidant therapy and dynamic monitoring. These materials are poised to become a critical engine driving precision medicine in oxidative-stress-related disorders. For this reason, it facilitates interventions characterized by more individualized, dynamically regulated and safely controllable design.
Over the past decade, immunotherapy has emerged as the fourth pillar of cancer therapy, following surgery, chemotherapy, and radiotherapy. However, tumors often evade immune responses by altering the tumor microenvironment (TME), which recruits immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages, and regulatory T cells. Among these, MDSCs are considered key contributors to immunotherapy failure and have become major targets in new therapeutic strategies. Growing evidence indicates that controlling MDSCs is critical to the success of cancer immunotherapy, and several drug classes have shown feasibility. In this review, we introduce the significance of MDSCs as a target in cancer immunotherapy and highlight different therapeutic approaches to counteract their immunosuppressive functions. We discuss recent efforts to optimize drug delivery for controlling MDSCs, focusing on resiquimod (R848) as a representative drug candidate.
Polymeric drug formulations have significantly improved the safety, efficacy, and clinical impact of many therapies. A persistent challenge for formulation scientists, however, lies in accurately characterizing time-dependent drug release. For decades, researchers have relied on mathematical and physical principles, with a focus on transport phenomena, to interpret release kinetics from various polymeric systems using mechanistic and empirical models. While these models provide a foundational understanding through equations relating diffusion, swelling, and erosion, they often depend on simplifying assumptions and are often limited to a retrospective analysis of in vitro data. Recent advances in artificial intelligence (AI) have since opened the door for a new frontier in modeling strategies. Specifically, machine learning (ML) is being used not only to characterize drug release but also predict it while unveiling key formulation parameters governing unique kinetic profiles. This approach can support faster and more efficient development of polymeric systems. In this review, we explore how traditional drug release models have set the stage for ML in drug delivery research. We discuss important trends across recent ML applications, including data compilation, processing, architecture selection, and performance metrics. This perspective aims to provide scientists with a practical roadmap of ML applications used in formulation development. By integrating these tools with established knowledge, researchers can advance the design and translation of the next generation of polymer-based drug delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Restoring long-distance spinal cord connectivity remains a major challenge in regenerative medicine. Despite advances in stem cell therapy, biomaterial scaffolds, and neuromodulation, recovery after spinal cord injury (SCI) is limited by a hostile post-injury microenvironment marked by chronic inflammation, glial scarring, and extracellular matrix (ECM) stiffening. This Perspective proposes nanoengineered niclosamide, a repurposable multi-pathway modulator, as a strategy to reprogram this niche. By attenuating NF-κB/STAT3-driven inflammation, suppressing fibrotic signaling, and reducing ECM rigidity, nanoengineered niclosamide may synergize with scaffold- and stimulation-based approaches, highlighting microenvironmental modulation as a realistic path forward for SCI repair.
Zoonotic diseases pose significant global health threats, with microbial pathogens, including bacteria, viruses, fungi, and protozoa, responsible for severe outbreaks. The rapid identification and control of zoonotic pathogens remain a major challenge due to their complex transmission dynamics and environmental persistence. Recent advances in molecular microbiology, nanotechnology, and artificial intelligence (AI) have revolutionized diagnostic and therapeutic strategies, enhancing the detection, monitoring, and prevention of diseases caused by pathogens. In machine learning (ML), it is possible to predict outbreaks and classify pathogens with high precision using genomic, proteomics, and epidemiological data, which can be analyzed with machine learning methods. Molecular-level detection is possible with nanotechnology-based biosensors, enabling rapid diagnosis even in areas with limited resources. Machine learning-driven computational models and nanotechnology-based detection tools can drive further advancements in microbial diagnostics, zoonotic disease surveillance, and host-pathogen interactions. Bioinformatics will be discussed along with new trends in microbial resistance and molecular mechanisms underlying pathogen identification in relation to zoonotic spillover events. By combining artificial intelligence with nanoscale biosensors, microbiology can develop more effective diagnostic platforms, real-time surveillance tools, and targeted antimicrobials. The standardization of data, the elimination of biosafety concerns, and the development of regulatory frameworks are all essential steps in advancing this cutting-edge approach to controlling zoonotic disease. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Liver fibrosis (LF), a major global health burden causing over two million deaths annually, arises from chronic injury leading to hepatic stellate cell (HSC) activation and pathological extracellular matrix (ECM) deposition. Current therapies are limited by nonspecific biodistribution and inadequate drug delivery to HSCs. Nanosystems engineered for active HSC targeting offer a promising approach to overcome fibrotic barriers—including capillarized sinusoids and dense ECM—through strategies such as receptor-specific ligand modification, RNA-based gene silencing, and multifunctional combinatorial therapies. These platforms enable precise modulation of HSC activation and ECM remodeling, promoting fibrosis regression while sparing healthy tissue. Despite promising preclinical outcomes, key challenges remain in biosafety, scalable fabrication, and clinical validation. Advancements in HSC-specific nanotherapeutics hold transformative potential for reversing liver fibrosis and restoring hepatic function. This article is categorized under:
The precise monitoring of specific inflammatory biomarkers is crucial for the accurate diagnosis and management of inflammation and infections, as well as for determining the most effective treatment. Recently, there has been a growing interest in innovative methods employing optical biosensors based on plasmonic nanoparticles (PNPs) for the detection of specific biomarkers. PNPs enable the translation of molecular recognition into results that are simple, fast, reliable, real-time, and easy to interpret. This review explores the studies published in recent years that focus on the development of apta- or immuno-sensors for the detection of inflammatory biomarkers. Focusing on diverse analysis techniques, including colorimetry, localized surface plasmon resonance, surface-enhanced Raman spectroscopy, fluorescence, chemiluminescence, and electrochemiluminescence, this review provides a comprehensive investigation of their applications in the detection of inflammatory biomarkers such as interleukins, procalcitonin, and C-reactive protein. For each method, advancements in sensor design, sensitivity, and specificity are reported. This article is categorized under: Diagnostic Tools > Biosensing.
Self-organizing tissues, such as organoids, offer transformative potential beyond healthcare by enabling the sustainable production of advanced materials. Resource scarcity and global warming drive the need for innovative fabrication solutions. This prospective review explores developmental biology as a manufacturing process, where the material (e.g., spider silk) and its production unit are self-organized (e.g., silk glands). Biological systems orchestrate the emergence of hierarchical materials with superior mechanical properties and biodegradability, using abundant and renewable resources. Tissue engineering enables the creation of biological systems that surpass current synthetic designs in complexity. We highlight application opportunities, focusing on spider silk as a model to demonstrate how organs synthesize and assemble next-generation materials. The concept of growing both a material and its organ production units is exemplified by hair-bearing organoids, self-organized from induced pluripotent stem cells (iPSCs). Key challenges in expanding organoid research to new model species and scaling-up production are discussed alongside potential solutions. We propose a simplified description of these complex systems to help address key challenges. Furthermore, synthetic and hybrid approaches are explored, considering the ethical, societal, and technological impacts. Though still in their infancy, material-producing organoids present a promising avenue for sustainable, high-value products, fostering new interdisciplinary collaborations among bioengineers, developmental biologists, and material scientists. This work aims to inspire further exploration into the applications of self-organized biological systems in addressing global challenges. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Nanotechnology Approaches to Biology > Cells at the Nanoscale.
Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed cancer treatment by achieving durable responses in a subset of patients. However, the effectiveness of ICIs is often limited by factors such as low tumor expression of PD-L1 and low tumor mutational burden, which contribute to immune evasion in "cold" tumors. Cancer vaccination through the delivery of tumor antigens offers a promising strategy to enhance antigen-specific immune priming and improve the responses to ICIs. Despite this potential, peptide-based cancer vaccines face several challenges, including immune tolerance, insufficient antigen delivery and presentation, and the immunosuppressive tumor microenvironment. To overcome these barriers, novel platforms are being developed to codeliver antigens with immunostimulatory agents. In this review, we highlight recent advances in peptide-based cancer vaccine design, including innovative materials, adjuvants, targeting strategies, and controlled release mechanisms. We also discuss their translation and how these approaches may ultimately expand the benefit of immunotherapy to patients with treatment-refractory cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Peptide-Based Structures Biology-Inspired Nanomaterials > Lipid-Based Structures.
Biosensors are the prototypes of future miniaturized and handheld devices that can quantitatively detect the analyte with reliable results. Electrochemical biosensors are a class of biosensors that are capable of both sensitive and selective detection and miniaturization, and the applications of nanomaterials in the electrochemical biosensor area are intriguing for the researchers who aim to overcome the analytical and miniaturization issues of the biosensors. In this review, electrochemical biosensors designed using nucleic acids as the biorecognition elements, namely electrochemical genosensors, were handled, and the recent developments in this area using nanoparticles were elaborately evaluated. Metal and carbon nanoparticle-based electrochemical genosensors for the detection of nucleic acids were summarized in tables, and the pros and cons of the fabrication of these genosensors regarding the analytical metrics and environmental concerns were explained through example studies reported in the literature. The greenness parameter of the nanoparticle-based electrochemical genosensors that indicates the environmental sustainability was discussed using the Analytical Greenness Calculator (AGREE), and the translational impacts of the implementation of nanoparticles in combination with artificial intelligence (AI) towards the electrochemical genosensor technology were evaluated. It could be concluded that the use of nanoparticles for the development of electrochemical genosensors can contribute to fabricating miniaturized and sustainable electrochemical devices with enhanced analytical properties. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > Diagnostic Nanodevices.
