Search Results (443)

Nanoparticles offer a versatile platform for the selective eradication of pathogenic or diseased cells by integrating therapeutic payload delivery with precision targeting. Precision targeting can be achieved (1) actively through ligand conjugation, (2) passively by exploiting the physiological abnormalities of diseased tissues, or (3) intrinsically through the innate biophysical properties of the nanoparticle. Intrinsically selective nanoplatforms (iNPs) are particularly advantageous when the disease-promoting agent does not possess distinct surface markers, such as in the case of certain “untargetable cancers” or cancers without known targets. Indeed, nanocarriers for chemotherapeutic or gene delivery have achieved selective cancer cell apoptosis without requiring marker presentation, thereby expanding the therapeutic window of the payload. Disease-promoting agents whose physical properties are different from those of healthy cells are also good candidates for intrinsic nanoparticle targeting. For example, antimicrobial nanomaterials have been designed to disrupt bacterial membranes and reduce the risk of antimicrobial resistance by leveraging stiffness differentials between bacterial cell walls and eukaryotic membranes. Nanoparticle systems with intrinsic targeting mechanisms can also enable non-invasive imaging with near-infrared fluorescence, MRI, and photoacoustic imaging for real-time biodistribution tracking and treatment monitoring. This review synthesizes current innovations in nanoplatform design with intrinsic targeting capabilities, spans applications in infectious and non-communicable diseases, and discusses emerging strategies to enhance specificity, overcome resistance, and translate these platforms toward clinical and field deployment. Full article

Lipid nanoparticles (LNPs) have become an important platform for the delivery of RNA therapeutics, including messenger RNA (mRNA) and small interfering RNA (siRNA). However, most clinically approved LNP formulations exhibit strong liver tropism following systemic administration, which limits efficient delivery to extrahepatic tissues. This inherent biodistribution profile has therefore been recognized as a key challenge for expanding the therapeutic applications of RNA nanomedicine. Recent efforts have focused on engineering functionalized LNP systems to improve delivery specificity beyond the liver. Surface modification with targeting ligands—such as antibodies, peptides, and nucleic acid aptamers—can promote receptor-mediated uptake by specific immune cell populations, including macrophages, dendritic cells and T lymphocytes. In parallel, advances in lipid design have improved intracellular RNA delivery by facilitating endosomal escape. These developments have broadened the potential use of RNA nanomedicine for inflammatory disorders, including autoimmune diseases, neuroinflammation, and cardiovascular inflammation. Functionalized LNPs are also being investigated for in vivo engineering of immune cells. This review summarizes current strategies for designing functionalized LNP systems, highlights their emerging applications in immune and inflammatory diseases, and discusses key challenges for clinical translation. Full article

Iron-based nanoparticles, particularly iron oxide nanostructures (IONPs), have emerged as versatile and clinically relevant platforms for drug delivery and theranostic applications. Among these, superparamagnetic iron oxide nanoparticles (SPIONs), including magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are the most extensively investigated due to their biocompatibility, magnetic responsiveness, and established safety profiles. Their unique superparamagnetic behavior enables external magnetic-field-guided targeting, magnetic resonance imaging (MRI) contrast enhancement, and magnetically triggered hyperthermia, enabling simultaneous diagnosis and therapy. Surface functionalization with polymers, silica, lipids, peptides, and biomolecules further improves colloidal stability, circulation time, targeting specificity, and controlled drug release. Core–shell architectures and multifunctional hybrid systems have expanded the therapeutic scope of iron nanoparticles, integrating chemotherapy, gene delivery, photothermal therapy, and Fenton reaction–mediated catalytic therapy. Despite promising preclinical outcomes, challenges remain regarding long-term biosafety, oxidative stress induction, biodistribution, large-scale reproducibility, and regulatory translation. This review summarizes the physicochemical properties, synthesis strategies, surface-engineering approaches, drug-loading mechanisms, and biomedical applications of iron-based nanoparticles, highlighting recent advances in multifunctional and peptide-functionalized systems. Critical considerations for clinical translation and future perspectives in precision nanomedicine are also discussed. Full article

CRISPR–Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targeted lipid nanoparticles (LNPs) for liver-derived targets such as transthyretin and plasma prekallikrein (KLKB1). As translation expands across hematologic, metabolic, ocular and oncology indications, development is increasingly constrained by the predictability and safety of editing outcomes, delivery-determined biodistribution and exposure time, and immune recognition of bacterial Cas9 orthologs and delivery components. We summarize diagnostic readouts for confirming patient genotype, quantifying on-target editing and expression changes, assessing off-target and structural outcomes using orthogonal assays, and monitoring clonal dynamics and immune responses during long-term follow-up. We also discuss how these readouts interface with CMC controls and regulatory expectations for advanced therapy medicinal products (ATMPs), highlighting the need for fit-for-purpose, standardized testing frameworks in early trials. Full article

Nanomaterials are emerging versatile platforms for therapeutic delivery, as they offer precise control over drug, antioxidant, and genetic payload transport across biological barriers. Inorganic, organic, hybrid, and biomimetic systems are the major classes of nanomaterials, which all have different physicochemical properties such as size, surface charge, and surface functionalization. These properties collectively influence stability, biodistribution, cellular uptake, and release kinetics. Engineering strategies are increasingly using stimuli-responsive designs that are triggered by pH, reactive oxygen species (ROS), and intracellular redox gradients to perform spatially and temporally controlled delivery. Antioxidant and redox-modulating nanocarriers are of great importance as they overcome the limited bioavailability and nonspecific activity of conventional antioxidants by improving stability, targeting oxidative microenvironments, and allowing for regulated release. Improvements in lipid, polymeric, and inorganic nanoplatforms have also developed gene delivery applications, including siRNA, mRNA, and CRISPR/Cas systems, to provide better cytosolic release and precise therapeutics. When diagnostic imaging is integrated with therapy through theranostic nanoparticles, real-time monitoring and personalized intervention are possible. Safety, scalable manufacturing, and regulatory alignment are some challenges that show the need for standardization and translational procedures to utilize the potential of theranostic nanomedicine. Full article

Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive oxygen species generation, activation of neuroinflammatory pathways, mitochondrial dysfunction, and disruption of blood–brain barrier integrity. These molecular events collectively lead to synaptic impairment, neuronal apoptosis, and progressive cognitive and behavioral deficits, with toxicity severity influenced by dose, exposure duration, and age. Given that in vitro models often fail to capture complex systemic interactions such as nanoparticle biodistribution, blood–brain barrier dynamics, and neuroimmune responses, this review places particular emphasis on in vivo studies to provide a more physiologically relevant understanding of nanoparticle-induced neurotoxicity. Importantly, a growing body of in vivo evidence demonstrates that natural bioactive compounds can mitigate these effects by targeting key pathogenic pathways, including oxidative stress, inflammation, and mitochondrial dysfunction, while preserving neuronal integrity. These findings highlight the therapeutic potential of natural bioactives as protective agents against nanoparticle-induced neurotoxicity and as candidates for broader neuroprotective strategies. This review summarizes the mechanistic basis of metal and metal oxide nanoparticle neurotoxicity and critically evaluates the protective role of natural bioactive compounds, with a focus on evidence derived from animal models. Full article

In search of a non-surgical alternative for male animal sterilization, this study investigated the use of gold-coated maghemite nanoparticles (γ-Fe₂O₃@Au) functionalized with citrate to produce testicular photohyperthermia (PHT). Wistar rats received an intratesticular injection of the fluid containing the nanoparticles (150 µL/testicle) followed by testicular irradiation with an LED light (808 nm). Testicular temperature was maintained at ~45 °C for 15 min. The results demonstrated a significant reduction in testicular volume and weight and sperm motility and normal morphology in PHT-treated animals, together with histopathological degeneration of seminiferous tubules. No treatment-related side effects or signs of systemic toxicity were observed. The biodistribution of the gold (Au) and iron (Fe) from the nanoparticles showed that the testes were the primary site of nanoparticle accumulation until day 56 post-treatment with possible renal excretion of Au. These findings support the prospect of testicular PHT mediated by γ-Fe₂O₃@Au nanoparticles as a neutering method for male animals. Full article

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine. Full article

Neuroinflammation is a central hallmark of numerous neurological disorders, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and spinal cord damage. Its persistent and dysregulated nature not only accelerates neuronal loss but also impedes endogenous repair, posing a major challenge for effective therapeutic intervention. Recent advances in nanobiotechnology have opened transformative opportunities to modulate neuroinflammation with unprecedented precision while simultaneously supporting neural regeneration. This review highlights emerging nanomaterial-based strategies including lipid-based, polymeric, inorganic nanoparticles designed to traverse the blood–brain barrier (BBB), deliver anti-inflammatory agents, modulate immune cell behavior, and attenuate glial activation. Extending beyond nanoparticle-based delivery systems, recent advances also emphasize the integration of nanomaterials into biomimetic architectures to provide structural and functional cues for neural repair. We further summarize how these functional nanostructured scaffolds, such as extracellular matrix (ECM) mimetic, nanofibrous and conductive hydrogels, are being leveraged in neural tissue engineering to direct stem cell fate, promote axonal outgrowth, and rebuild damaged neuroarchitectures. Moreover, pharmacokinetics, biodistribution, safety, clinical trials, regulatory considerations and limitations of nanotherapeutics in neurodegenerative diseases are discussed. By outlining the current progress, mechanistic insights, and translational challenges, this review underscores the potential of nanobiotechnology-enabled therapeutics to revolutionize the treatment of neuroinflammatory conditions and advance next-generation neural repair technologies. Full article

Background/Objectives: Magnetite nanoparticles represent promising candidates for a broad spectrum of biomedical applications, ranging from in vitro diagnostic assays to in vivo imaging, hyperthermia, and targeted drug and gene delivery, with some nanoagents already approved for clinical use. A critical determinant of their functionality is the nanoparticle coating, which facilitates beneficial interactions within biological systems. In the context of tumor-targeted therapeutic delivery, key design parameters—particularly surface coatings—can be optimized to enhance treatment efficacy by modulating blood circulation kinetics, biodistribution, and other critical properties. However, current preclinical screening methods primarily rely on cell culture models to identify potential nanocarriers, yet these systems often poorly correlate with actual in vivo performance. This discrepancy highlights the necessity of incorporating more biologically relevant testing platforms, such as high-throughput in vivo assays. Methods: In this work, we employed an original magnetic particle quantification (MPQ) technology to systematically evaluate the blood circulation kinetics and biodistribution patterns for magnetite nanoparticles with 17 different coatings across multiple organs and tissues, including the liver, spleen, lungs, kidneys, heart, tumor, brain, peripheral blood, muscle, and bone. This methodology offers high sensitivity, user-friendly operation, and provides quantitative measurements across a broad dynamic range of nanoparticle concentrations. These advantages enabled high-throughput acquisition of precise blood circulation and biodistribution data. In addition, histological analysis was conducted to evaluate nanoparticle penetration depth within tumor tissue. Results: Here we conducted a comprehensive study of the effect of 17 different polymer-, lectin-, and small molecule-based coatings on the behavior of magnetite nanoparticles in vivo. For each type of obtained nanoparticles, we implemented passive targeting as well as magnetic targeting, the latter using an external magnetic field localized in the tumor area. Conclusions: The collected dataset provides critical insights into how surface modifications influence nanoparticle performance in complex biological systems, offering valuable guidance for optimizing therapeutic nanocarrier design. Full article

“Smart” nanoparticles are often presented as the vanguard of precision cancer therapy, defined by engineered abilities to sense predefined stimuli, enhance targeting, and control therapeutic release. Yet this notion of smartness remains largely material-centric and only partially reflects how nanomedicines behave in vivo. Cells exposed to nanoparticles are not passive recipients of engineered functions; they actively interpret these perturbations through integrated stress-response, metabolic, transcriptional, and innate immune programs. These cell-state trajectories can determine efficacy, tolerance, resistance, or toxicity, and can do so independently of uptake, biodistribution, or triggerable release efficiency. Accordingly, evaluation strategies that prioritize delivery metrics and limited a priori molecular markers may misestimate functional performance and durability. This Perspective proposes a cell-aware reframing in which smartness is defined by biological controllability: the capacity of a nanoparticle system to elicit predictable, mechanistically interpretable, and therapeutically favorable cell-state trajectories across relevant malignant and non-malignant compartments. A practical path forward is to integrate time-resolved functional profiling into benchmarking using compact response signatures that report stress buffering, immune activation or suppression, and the emergence of tolerant states. A practical path forward is to integrate time-resolved functional profiling into benchmarking using compact response signatures that report stress buffering, immune activation or suppression, and the emergence of tolerant states. Here, biological controllability refers to the ability of a nanoparticle system to reproducibly steer integrated cellular stress, metabolic, and immune programs toward predefined therapeutic endpoints while minimizing adaptive escape across heterogeneous compartments. Full article

Glioblastoma (GBM) is the most common malignant primary brain tumor among adults and one of the deadliest human cancers. Its infiltrative growth pattern, high intratumor heterogeneity, and the existence of the blood–brain barrier severely limits current treatment approaches. Precision medicine-guided treatment decision-making based on unique molecular characteristics of patients’ tumors and tumor microenvironments is highly desired. Gold nanoparticles (AuNPs) are promising nanoplatforms that enable precision medicine and personalized treatments for GBM. Their size- and shape-dependent tunable physiochemical properties, ease of surface functionalization, unique optical/electronic properties, and biocompatibility have facilitated the development of AuNP-based multimodal agents with the capability of delivering therapies, molecular imaging, and diagnosis in one platform. Recent research has shown that AuNPs can deliver chemotherapeutics, genes, and immunotherapeutics and aid in imaging, radiosensitization, and photothermal therapy for GBM therapy. Ligand-targeted and stimuli-responsive AuNPs enable site-selective targeting of GBM cells and the tumor microenvironment, allowing for personalized medicine approaches. Here, we review the progress made in biomedical applications of AuNPs for GBM treatment with a focus on precision-based drug/gene delivery, diagnosis/imaging, and therapy enhancement. We also discuss safety, biodistribution, scalability for translation, and regulatory challenges that need to be addressed for AuNP development. Future opportunities for AuNPs in personalizing GBM treatment are also highlighted. Full article

Solid lipid nanoparticles (SLNs) are submicron colloidal systems widely investigated as drug carriers; however, their intrinsic biodistribution properties are also critical when SLNs are considered for diagnostic imaging. In the present proof-of-concept study, drug-free SLNs were evaluated exclusively as a radiolabeled imaging agent rather than as a drug delivery system. SLNs were radiolabeled with Technetium-99m (^99mTc), and their in vivo biodistribution was investigated using gamma camera imaging, ex vivo organ counting, and confocal microscopy. SLNs were prepared by a microemulsion–low-temperature solidification method and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Radiolabeling efficiency was determined by instant thin-layer chromatography (ITLC) and exceeded 95%. Following intravenous administration in a rabbit model, dynamic scintigraphic imaging demonstrated predominant uptake in the liver and spleen. These findings were quantitatively confirmed by ex vivo biodistribution analysis at 4 h post-injection and qualitatively supported by confocal microscopy of liver and spleen tissues. The results indicate that ^99mTc-labeled SLNs behave as RES-targeting radiocolloids and may serve as potential agents for liver–spleen scintigraphy. Full article

Acute and chronic kidney diseases remain significant challenges in regenerative medicine, with few therapies capable of reversing tissue injury or preventing progression. Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) are nanosized vesicles (30–150 nm) that have emerged as multifunctional nanotheranostic platforms, combining targeted therapeutic activity with imaging-enabled monitoring. In renal pathophysiology, BM-MSC-Exos exert anti-inflammatory, anti-fibrotic, angiogenic, and pro-regenerative effects. These actions are mediated by microRNAs, messenger RNAs, mitochondrial regulators, and bioactive proteins that modulate epithelial repair and immune responses. Recent bioengineering advances enable more precise BM-MSC-Exos design, including enrichment with synthetic RNAs or gene-editing components and membrane functionalization to enhance kidney tropism. In parallel, fluorescence, bioluminescence, and nanoparticle-based approaches support in vivo tracking. These tools allow real-time assessment of biodistribution and tubular uptake, strengthening evidence for target engagement. This review synthesizes current knowledge on BM-MSC-Exos in renal repair. We summarize contemporary strategies for cargo and surface engineering, outline imaging methodologies for in vivo tracking, and discuss how administration routes influence renal targeting. We also provide an updated overview of clinical trials evaluating exosomes as therapeutic agents or biomarkers in nephrology. Collectively, engineered BM-MSC-Exos represent a promising and increasingly sophisticated platform for precision-guided kidney therapy, supported by monitoring tools that facilitate preclinical evaluation of biodistribution and efficacy. Full article

Boron neutron capture therapy (BNCT) is experiencing a global resurgence driven by advances in boron pharmacology, accelerator-based neutron sources, and molecular imaging-guided theranostics. BNCT produces high linear energy transfer particles with micrometer-range energy deposition, enabling cell-selective irradiation confined to boron-enriched tumor cells in a geometrically targeted region by the neutron beam. This mechanism offers the potential for exceptionally high therapeutic ratios, provided two core requirements are met: sufficient differential tumor uptake of ¹⁰B and a neutron beam with appropriate energy and penetration. After early clinical attempts in the mid-20th century were hindered by inadequate boron agents and reactor-based neutron beams, recent technological breakthroughs have made BNCT clinically viable. The development of hospital-compatible accelerator neutron sources, next-generation boron delivery systems (such as receptor-targeted compounds and nanoparticles), advanced theranostic approaches (such as ¹⁸F-BPA positron emission tomography and boron-sensitive magnetic resonance imaging), and AI-driven biodistribution modeling now support personalized treatment planning and patient selection. These innovations have catalyzed modern clinical implementation, exemplified by Japan’s regulatory approval of BNCT for recurrent head and neck cancer and the rapid expansion of clinical programs across Asia, Europe, and South America. Building on these foundations, BNCT has transitioned from a predominantly academic experimental modality into an increasingly commercialized and industrially supported therapeutic platform. The emergence of dedicated BNCT companies, international collaborations between accelerator manufacturers and hospitals, and pharmaceutical development pipelines for next-generation boron carriers has accelerated clinical translation. Moreover, BNCT now occupies a unique position among radiation modalities due to its hybrid nature, namely combining the biological targeting of radiopharmaceutical therapy with the external-beam controllability of radiotherapy, thereby offering new therapeutic opportunities where competitive approaches fall short. Emerging evidence suggests therapeutic promise in glioblastoma, recurrent head and neck cancers, melanoma, meningioma, lung cancer, sarcomas, and other difficult-to-treat malignancies. Looking ahead, continued innovation in compact neutron source engineering, boron nanocarriers, multimodal theranostics, microdosimetry-guided treatment planning, and combination strategies with systemic therapies such as immunotherapy will be essential for optimizing outcomes. Together, these converging developments position BNCT as a biologically targeted and potentially transformative modality in the era of precision oncology. Full article