Search Results (87)

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

Carbon dots (CDs) have emerged as a distinct class of fluorescent nanomaterials distinguished by their tunable physicochemical properties, ultrasmall size, exceptional photoluminescence, versatile surface chemistry, high biocompatibility, and chemical stability, positioning them as promising candidates for biomedical applications ranging from sensing and imaging to drug delivery and theranostics. As CDs increasingly transition toward biological and clinical use, a fundamental understanding of their interactions with biological membranes becomes essential, as cellular membranes govern nanoparticle uptake, intracellular transport, and therapeutic performance. Model membrane systems, such as phospholipid vesicles and liposomes, offer controllable platforms to elucidate CD-membrane interactions by isolating key physicochemical variables otherwise obscured in complex biological environments. Recent studies demonstrate that CD surface chemistry, charge, heteroatom doping, size, and hydrophobicity, together with membrane composition, packing density, and phase behavior, dictate nanoparticle adsorption, insertion, diffusion, and membrane perturbation. In addition, CD-liposome hybrid systems have gained momentum as multifunctional nanoplatforms that couple the fluorescence and traceability of CDs with the encapsulation capacity and biocompatibility of lipid vesicles, enabling imaging-guided drug delivery and responsive theranostic systems. This review consolidates current insights into the mechanistic principles governing CD interactions with model membranes and highlights advances in CD-liposome hybrid nanostructures. By bridging fundamental nanoscale interactions with translational nanomedicine strategies, this work provides a framework for the rational design of next-generation CD-based biointerfaces with optimized structural, optical, and biological performance. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

Brain metastases have a distinctive vascular ecosystem—shaped by sprouting angiogenesis, vessel co-option, vasculogenic mimicry, and tumor cell transdifferentiation—that governs tumor perfusion, drug exposure, and therapeutic responsiveness. These heterogeneous vascularization patterns exhibit characteristic differences in enhancement morphology, perfusion levels, and metabolic uptake on contrast-enhanced MRI, perfusion imaging, and amino acid PET, providing crucial imaging cues for identifying routes of blood supply, inferring the state of the blood–tumor barrier, and guiding individualized therapeutic strategies. Anti-VEGF therapy is primarily used to alleviate cerebral edema and radiation necrosis, yet it confers limited survival benefit, underscoring the spatiotemporal heterogeneity of the blood–tumor barrier and the persistence of non-classical vascularization pathways. Building on the concept of “vascular normalization,” combinations of anti-angiogenic therapy with immunotherapy, radiotherapy, or targeted agents have shown encouraging intracranial activity in selected settings—most robustly in melanoma brain metastases—but remain insufficiently validated in randomized, brain-metastasis-focused trials. By integrating mechanistic, imaging, and therapeutic perspectives, this review outlines how vascular-ecosystem-based stratification and physics-informed drug-delivery strategies may help transition anti-vascular therapy from symptomatic control toward mechanism-driven precision intervention. Full article

Background/Objectives: Nanoparticles have emerged as indispensable tools in modern biomedicine, enabling precise diagnostics, targeted therapy, and controlled drug delivery. Despite their rapid progress, the translation of nanoparticle-based systems critically depends on the ability to detect, quantify, and track them across complex biological environments. Over the past two decades, a wide spectrum of detection modalities has been developed, encompassing optical, magnetic, acoustic, nuclear, cytometric, and mass spectrometric principles. Yet, no comprehensive framework has been established to compare these methods in terms of sensitivity, spatial resolution, and clinical applicability. Methods: Here we show a systematic analysis of all broadly applicable nanoparticle detection strategies, outlining their mechanisms, advantages, and drawbacks, and providing illustrative examples of practical applications. Results: This comparison reveals that each modality occupies a distinct niche: optical methods offer high sensitivity but limited penetration depth; magnetic and acoustic modalities enable repeated non-invasive tracking; nuclear imaging ensures quantitative, whole-body visualization; and invasive biochemical or histological assays achieve ultimate detection limits at the cost of tissue integrity. These findings redefine how each technique contributes to nanoparticle biodistribution and mechanistic studies, clarifying which are best suited for translational and clinical use. Conclusions: Placed in a broader context, this review bridges fundamental nanotechnology with biomedical applications, outlining a unified methodological framework that will guide the rational design, validation, and clinical implementation of nanoparticle-based therapeutics and diagnostics. By synthesizing the field into a single comparative framework, it also provides an accessible entry point for newcomers in nanotechnology and related biomedical sciences. Full article

Smart vesicle therapeutics represent a transformative frontier in nanomedicine, offering precise, biocompatible, and adaptable platforms for drug delivery and theranostic applications. This review explores recent advances in the design and engineering of liposomes, niosomes, polymersomes, and extracellular vesicles (EVs), emphasizing their capacity to integrate therapeutic and diagnostic functions within a single nanoscale system. By tailoring vesicle size, composition, and surface chemistry, researchers have achieved improved pharmacokinetics, reduced immunogenicity, and fine-tuned control of drug release. Stimuli-responsive vesicles activated by pH, temperature, and redox gradients, or external fields enable spatiotemporal regulation of therapeutic action, while hybrid bio-inspired systems merge synthetic stability with natural targeting and biocompatibility. Theranostic vesicles further enhance precision medicine by allowing real-time imaging, monitoring, and adaptive control of treatment efficacy. Despite these advances, challenges in large-scale production, reproducibility, and regulatory standardization still limit clinical translation. Emerging solutions—such as microfluidic manufacturing, artificial intelligence-guided optimization, and multimodal imaging integration—are accelerating the development of personalized, high-performance vesicular therapeutics. Altogether, smart vesicle platforms exemplify the convergence of nanotechnology, biotechnology, and clinical science, driving the next generation of precision therapies that are safer, more effective, and tailored to individual patient needs. Full article

Synergetic therapeutic study using multifunctional nanoplatforms has been developed as an innovative modality for effective cancer treatment to improve the clinical efficiency of anticancer drugs and reduce severe off-target side effects. Herein, an artificial nanoplatform (denoted as PPy-RhB-PDA-CD-LA) was prepared by grafting β-cyclodextrin (β-CD) derivatives and lactobionic acid (LA) on the surface of rhodamine B (RhB)-doped polypyrrole nanoparticles (PPy-RhB NPs) using polydopamine (PDA) as the intermediate linker. Doxorubicin (DOX) was selected and successfully loaded onto the nanoplatforms with a high loading content of 327 mg/g. Furthermore, significant NIR light-triggered release of DOX was observed in a weak acidic tumor microenvironment. The nanoplatform exhibited superior photostability with a high photothermal effect of 51.7% under irradiation by a 808 nm laser and a competent temperature sensitivity (SR is 1.44% °C⁻¹) under a single wavelength excitation. MTT assay against SMMC-7721 cells clearly illustrated that the nanoplatform had low cytotoxicity at a high level (200 μg/mL) after 24 h and high therapeutic efficacy of chemo-phototherapy. Thus, it is highly promising for use in biomedical applications. Full article

The advent of nanotechnology has revolutionized the field of medicine, particularly in the development of targeted therapeutic strategies. Among these, radiolabeled nanomaterials have emerged as promising tools for both diagnostic and therapeutic applications, offering precise delivery of radiation to diseased tissues while minimizing damage to healthy ones. Notably, Lutetium-177 (¹⁷⁷Lu) has gained significant attention due to its favorable emission properties and availability that render it suitable for imaging and therapeutic purposes. When integrated with magnetic nano-formulations, ¹⁷⁷Lu-labeled systems combine the benefits of targeted radiation therapy (TRT) with the unique properties of magnetic nanoparticles (MNPs), such as magnetic resonance imaging (MRI) contrast enhancement and magnetically guided drug delivery to address challenges in diagnosis and treatment of diseases, such as cancer. By examining the latest advancements in their design, particularly surface functionalization and bioconjugation strategies, this study aims to highlight their efficacy in targeted therapy, imaging, and theranostic applications. Furthermore, we discuss the current challenges, such as scalability, biocompatibility, and regulatory hurdles, while proposing future directions to enhance their clinical translation. This comprehensive review underscores the transformative potential of ¹⁷⁷Lu-labeled magnetic nano-formulations in precision medicine and their role in shaping the future of therapeutic interventions. Full article

Diffuse intrinsic pontine glioma (DIPG), or as it is newly redefined, diffuse midline glioma (DMG), remains one of the most horrific diagnoses in pediatric oncology. Aggressive and inaccessible to standard treatments, it is generally considered incurable. Focused ultrasound technology has developed over the last several decades as a noninvasive means to target various types of tumors in both adults and children. Recent advances, particularly in low-intensity focused ultrasound (LIFU), have opened new avenues for enhancing drug delivery and modulating the tumor microenvironment in these challenging tumors. This review provides a comprehensive overview of preclinical and clinical research developments in the use of LIFU for pediatric DMGs. We highlight key findings from animal models demonstrating improved blood–brain barrier (BBB) permeability, increased chemotherapeutic and nanoparticle delivery, and potential immunomodulatory effects of LIFU. Emerging clinical studies, including early-phase safety and feasibility trials, are also discussed, with attention to technical parameters, imaging guidance strategies, and biomarkers of response. The review concludes by addressing the challenges of translating LIFU into routine clinical practice, including device optimization for pediatric anatomy, regulatory hurdles, and the need for standardized treatment protocols. Collectively, these recent advances underscore the promise of LIFU as a minimally invasive, image-guided adjunct to current and future therapies for pediatric DMGs, warranting continued research and collaborative clinical efforts. Full article

Lumbosacral radiculopathy is a frequent cause of lumbosacral pain in both dogs and humans. Targeted lumbosacral foraminal perineural injections (commonly referred to as transforaminal epidural injections) are described in dogs and are widely used in medicine to treat lumbosacral radicular pain. This cadaveric study evaluated the injectate distribution achieved by lumbosacral foraminal injections using a combined ultrasound- and fluoroscopy-guided technique to position the tip of the needle at the cranial aspect of the foramen. Ten injections were performed in five dog cadavers using a contrast-dye mixture, and distribution was assessed by fluoroscopy, CT imaging, and anatomical dissections. Perineural epidural staining of L7 at the foraminal region was achieved in 90% of injections, with transforaminal epidural spread medial to the intervertebral foramen in 80% of injections. Subarachnoid spread occurred in 50–60%, while vascular uptake was uncommon (10–20%). The technique enabled consistent needle placement, even when nerve visualisation was limited. These findings indicate that the method can reliably achieve perineural epidural staining of L7 while minimising vascular uptake, supporting its potential clinical utility for targeted drug delivery in dogs with lumbosacral radiculopathy. Further research is needed to validate safety and efficacy in live patients. Full article

Background/Objectives: Nasal biopharmaceutics is the scientific understanding of product and patient factors that determine the rate and extent of drug exposure following nasal administration. The authors considered whether current biopharmaceutics tools are fit for the current and future needs of nasal product development and regulation. Methods: The limitations of current methods were critically assessed, unmet needs were highlighted, and key questions were posed to guide future directions in biopharmaceutics research. Results: The emergence of physiologically based biopharmaceutics models for nasal delivery has the potential to drive the scientific understanding of nasal delivery. Simulations can guide formulation and device development, inform dose selection and generate mechanistic insights. Developments in modeling need to be complemented by advances in experimental systems, including the use of realistic or idealized nasal casts to estimate the regional deposition of nasal sprays and refined in vitro cell culture models to study nasal drug absorption and the influence of mucus. Similarly, improvements are needed to address the practicalities of using animals in non-clinical studies of nasal drug delivery, and greater clinical use of gamma scintigraphy/magnetic resonance imaging is recommended to measure the delivery and nasal retention of different formulations in humans. Conclusions: Nasal drug delivery is a rapidly growing field and requires advances in nasal biopharmaceutics to support product innovation. Key needs are (i) validated clinically relevant critical product attributes for product performance and (ii) established links between how patients administer the product and where in the nose it deposits and dissolves in order to act or be absorbed, leading to its desired clinical effect. Full article

Peptide nanofibers (PNFs) have emerged as versatile platforms for delivering therapeutic agents due to their biocompatibility, tunable characteristics, and ability to form well-ordered nanostructures. The primary goal of this review is to elaborate on the key features of common PNF fabrication strategies, including both spontaneous and non-spontaneous methods, while exploring how the amino acid sequences of these peptides influence their secondary structure and fiber formation. Additionally, we have compiled studies on PNFs that investigate various delivery approaches, such as systemic delivery, localized delivery, controlled delivery, stimuli-responsive delivery, and targeted delivery. This analysis aims to guide researchers in selecting the most suitable fabrication strategy for specific delivery applications and provide insights into choosing optimal amino acids for rational peptide design. We also focused on the applications of PNFs in delivering various therapeutic agents, including drugs, functional peptides, diagnostic and imaging agents, genes, viral vectors, and vaccines, demonstrating their significant potential in biomedical applications. The synergy between nanofiber fabrication strategies and peptide chemistries offers new avenues for advancing therapeutic products. Overall, this review serves as an important reference for the design and development of advanced PNFs for the effective delivery of various therapeutic agents. Full article

This review summarizes recent advances in photoactive nanomaterials containing metals and their biomedical applications, particularly in cancer diagnosis and therapy. Conventional approaches such as chemotherapy and radiotherapy suffer from low specificity, systemic toxicity, and resistance, while light-based therapies, including photothermal therapy (PTT) and photodynamic therapy (PDT), offer minimally invasive and localized alternatives. Metal nanomaterials, especially gold and silver, exhibit unique localized surface plasmon resonance (LSPR) effects that enable efficient light-to-heat or light-to-reactive oxygen conversion, supporting precise tumor ablation, drug delivery, and imaging. We discuss strategies for structural design, surface functionalization, and encapsulation to enhance stability, targeting, and therapeutic efficiency. Emerging hybrid systems, such as carbon-based nanostructures and metal–organic frameworks, are also considered for their complementary properties. Computational modeling tools, including finite element and discrete dipole approximations, are highlighted for predicting nanomaterial performance and guiding rational design. Finally, we critically assess challenges such as toxicity, long-term biocompatibility, and clinical translation, and provide perspectives for future development. By integrating materials design, simulation, and preclinical findings, this review aims to inform the advancement of safer and more effective nanotechnology-based platforms for personalized cancer treatment and diagnosis. Full article

Nanofluids (NFs), consisting of nanoparticles (NPs) suspended in base fluids, have attracted growing interest due to their superior physicochemical properties and multifunctional potential. In this review, conventional and green NF technology aspects, including synthesis routes, formulation, and applications, are discussed. Conventional NFs, involving NPs synthesized using physical and chemical approaches, have improved NP morphology control but are likely to cause environmental and safety concerns. In contrast, green NFs that are plant extract, microorganism, and biogenic waste-based represent a sustainable and biocompatible alternative. The effect of key parameters (e.g., NP size, shape, concentration, dispersion stability, and base fluid properties) on the performance of NFs is critically examined. The review also covers potential applications: in biomedical engineering (e.g., drug delivery, imaging, theranostics, and antimicrobial therapies), in heat transfer (e.g., solar collectors, cooling electronics, nuclear reactors), and precision machining (e.g., lubricants and coolants). Comparative insights regarding green versus conventionally prepared NFs are provided concerning their toxicity, environmental impact, scalability, and functional performance across various applications. Overall, this review highlights the new promise of both green and conventional NFs and provides key opportunities and challenges to guide future developments in this field. Full article

Small interfering RNAs (siRNAs) are particularly attractive among the frontier drugs due to their high specificity of action, activity on disease-inducing genes, and small molecular weight, thus being one of the most studied agents for gene therapy. However, siRNAs are prone to fast enzymatic degradation in the bloodstream, as well as other limitations that challenge their clinical translation. Nanoparticle (NP) delivery of siRNA has been proposed as a potential solution, overcoming their intrinsic limitations. In this regard, the siRNA delivery by magnetic nanoparticles is of particular interest because, being susceptible to external magnetic fields, it may be guided remotely, maximizing transfection efficiency and minimizing side effects. In addition, magnetic NPs would also allow a theranostic combination of drug delivery, magnetic resonance imaging, and hyperthermia. In this work we have studied the uptake of a model therapeutic siRNA by iron-doped hydroxyapatite nanoparticles (FeHA NPs), which are known to have excellent biocompatibility and magnetic susceptibility. We discovered that FeHA NPs stabilized by citrate (Cit-FeHA NPs) uptake siRNA by adsorption quickly and with high efficiency (ca. 90%) without altering nanoparticles physicochemical properties or colloidal stability. SiRNA-loaded Cit-FeHA NPs are able to slowly release their payload, with a sustained release of 45 days without siRNA degradation. Our work is therefore the preliminary validation of the suitability of FeHA NPs for magnetically guided delivery of therapeutic siRNAs. Full article