Drug delivery in cornea remains a challenge due to its unique dome shape, anatomy, epithelial barrier, rapid drug clearance, and eyelid blinking. Nanoscale-based drug delivery systems are particularly attractive for treating corneal diseases due to sustained local drug release without major side effects. Nano drug delivery systems have potential to overcome many limitations including drug's residence-time, controlled-release, and solubility in the cornea. This review provides an overview of critical considerations for corneal nanomedicine development ranging from the nanoscale-design to achieving an optimal drug delivery with a discussion on cornea-specific biology and diseases. Herein, we discuss key anatomical features and drug transport challenges across the tear film, mucins/glycocalyx, epithelium, stroma, and endothelium that can influence nanoparticle behavior. Further, article outlines indication-driven target drug profiling; core physicochemical parameters related to drug retention, penetration, distribution, and safety; and factors affecting sterility, osmolality, tolerability, and pH, regulatory expectations, and manufacturing reproducibility. Overall, nanoscale drug delivery systems offer an attractive approach to treat corneal dysfunction without major side effects.

Chirality critically governs the pharmacodynamics and clinical performance of small molecule drugs, yet its role in governing bio-nano interactions of synthetic polymeric nanocarriers has remained largely unexplored. Surface grafting with hydrophilic, biocompatible "stealth" polymers such as poly(ethylene glycol) (PEG) is a critical design strategy for nanomedicines intended to reduce nonspecific biological interactions and achieve prolonged circulation. However, the rising prevalence of anti-PEG antibodies has driven the search for fundamentally new design principles, mostly focused on substituting PEG with an entirely different polymer type. Poly(2-oxazoline)s (POx) constitute a versatile class of biocompatible synthetic polymers that uniquely enable access to numerous water-soluble macromolecules that can be rendered chiral, an attribute rarely accessible in synthetic stealth polymers. Here, we report the fabrication of crystalline-core nanorods bearing a chiral poly(2,4-dimethyl-2-oxazoline) (PdMeOx) corona via crystallisation-driven self-assembly (CDSA), and examine the influence of polymer chirality on biodistribution and antibody recognition in vivo. Well-defined enantiopure and racemic PdMeOx-b-poly(2-(isopropyl)-2-oxazoline) block copolymers were synthesised and assembled into short nanorods with distinct optical activities, enabling a detailed investigation of chirality-dependent bio-nano interactions. We demonstrate that polymer chirality induces the generation of enantiomer-specific antibodies, an effect that has not previously been reported for synthetic macromolecular nanomaterials. These findings reveal stereochemistry as an orthogonal design parameter for modulating immune interactions and suggest a future strategy in which alternating polymer chirality, rather than changing polymer type, can be exploited to mitigate antibody-mediated clearance through structured dosing regimens.

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.

Organ-selective immunomodulation is increasingly viewed as a route to improve the therapeutic index of cancer immunotherapy, yet most agents are still delivered systemically, where limited tumor exposure and immune-related toxicities remain common. The lung is an attractive site for local intervention because it is directly accessible and immunologically specialized. However, effective pulmonary delivery is constrained by mucociliary clearance, airway mucus, alveolar macrophage uptake, and epithelial barriers. Nanomaterials can be rationally engineered to address these constraints, increasing pulmonary retention and concentrating immunotherapeutics within the lung tumor microenvironment while reducing systemic burden. This Review summarized the key physiological barriers for pulmonary immunotherapeutic delivery and discusses how nanomaterial properties shape deposition, retention, cellular partitioning, and downstream immune activation. We critically evaluate representative inhalable platforms across major immunotherapeutic modalities, including vaccines, immune checkpoint blockade, innate immune agonists (e.g., STING agonists), cytokine regulation, and emerging in situ immune-cell engineering strategies. We also highlight translational considerations. Together, these advances support inhalable immunotherapeutic nanomedicines as a complementary approach to current lung cancer treatment and a broader framework for pulmonary immune modulation.

Quantum dots (QDs), owing to their unique optical properties and tunable surface functionalities, have emerged as powerful tools in biomedical research, particularly in diagnostics, drug delivery, and bioimaging. Among them, glutathione (GSH)-coated silver sulfide (Ag2S) QDs represent a promising class of biocompatible nanomaterials with near-infrared (NIR) fluorescence, making them highly suitable for biological applications. This chapter presents a novel approach utilizing GSH-coated Ag2S QDs as immobilized substrates and substrate analogues for the evaluation of glutathione-dependent enzymes glutathione reductase (GR) and glutathione S-transferase (GST). Through kinetic analyses, both purified enzymes and biologically relevant enzyme sources, such as rat liver lysate and cultured cell lysates, were employed to investigate the interaction efficiency and enzymatic activity with QD-bound GSH. The results demonstrated that GSH-coated QDs not only participate in enzyme-catalyzed redox cycling but also retain functionality comparable to free GSH or oxidized glutathione (GSSG), particularly under physiological conditions. Additionally, microscopic imaging confirmed the internalization of these QDs in mammalian cells, indicating their potential for in vivo enzymatic assays and theranostic applications. Overall, this study introduces a robust and innovative nanobiotechnological platform to explore enzyme-substrate interactions and redox regulation, with significant implications for biosensing, cancer research, and nanomedicine.

Tau PET imaging with [18F]flortaucipir allows for the visualization and mapping of aggregated tau deposits, a key neuropathologic feature of Alzheimer disease (AD). A visual interpretation method for [18F]flortaucipir was approved by the Food and Drug Administration and European Medicines Agency and has been implemented for a standardized, clinically usable definition of tau PET positivity. The CenTauRz method, on the other hand, offers the possibility to harmonize the definition of tau PET positivity across different radiotracers using quantitative metrics, but its concordance with clinically relevant [18F]flortaucipir visual reads remains unclear. Methods: A convenience sample of 3991 participants, including cognitively unimpaired (CU) and cognitively impaired (CI) individuals (i.e., those with mild cognitive impairment or AD dementia), underwent [18F]flortaucipir PET imaging. Each [18F]flortaucipir scan was assessed by 3 trained readers using the approved visual interpretation method and quantified using the CenTauRz quantification pipeline in different regions of interest (ROIs). Concordance between positive visual reads and CenTauRz-defined positivity (i.e., >2 on the CenTauRz scale) was assessed using Cohen κ. Receiver-operating-characteristic (ROC) analysis evaluated the discriminative power of continuous CenTauRz values in distinguishing between negative and positive visual reads. Generalized additive models examined clinical progression on the basis of visual and CenTauRz-based assessments of tau PET positivity. Results: Concordance between visual reads and CenTauRz-based assessments of tau PET positivity was moderate, particularly in CU individuals (κ = 0.23-0.55 for CU participants, κ = 0.57-0.82 for CI participants, depending on the ROI). ROC analysis revealed that the agreement remained moderate, independent of the CenTauRz cut point used (area under the ROC curve, 0.72-0.87 vs. 0.87-0.97 for CU and CI individuals, respectively). Among discordant cases, participants with visually positive/CenTauRz-negative tau PET scans were more frequently amyloid-positive and exhibited faster clinical progression compared with visually negative/CenTauRz-positive individuals. Conclusion: Our findings highlight the relatively limited agreement between the visual assessment of [18F]flortaucipir PET images and CenTauRz-based quantification, particularly in CU individuals. Participants with visually positive/CenTauRz-negative tau PET scans showed a high frequency of amyloid positivity and faster clinical progression, suggesting that visual reads are more sensitive to heterogeneous, clinically relevant tau accumulation patterns not captured by ROI-based methods. These findings underscore the need for new quantification approaches to better capture the complex patterns of tau deposition, important for early AD detection and monitoring.

Prostate cancer is one of the least immunogenic malignancies and poorly responds to immunotherapies. Characterized by an immunosuppressive tumor microenvironment and a scarcity of cytotoxic T-cell infiltrates, prostate cancer has been closely linked to extracellular vesicles (EVs), including exosomes and microvesicles, as important immunomodulators of immune evasion, therapy resistance, and disease progression. Through their cargo of proteins, lipids, and nucleic acids, tumor-secreted EVs shape antigen presentation, immune checkpoint activity, myeloid cell fate, and pre-metastatic niche formation by exchanging programmed death-ligand 1 (PD-L1), cytokines, microRNAs (miRNAs), and other bioactive mediators. These discoveries have led to EVs being investigated not only as a mechanism for prostate cancer aggressiveness but also as therapeutic targets themselves. Furthermore, engineering EVs for cancer therapy has become more prominent over recent years, as they are used as natural delivery vehicles for immunomodulatory drugs, nucleic acids, and toxins, as well as for the development of cancer vaccines. In this review, we discuss the EV-immune axis in prostate cancer and how chemotherapeutics, EV biogenesis inhibitors, and radionuclides reprogram EV-immune interactions. Engineered EVs, dendritic cell-derived EVs, and EV vaccines are also explored as potential immunotherapeutic opportunities. Overall, by targeting EV-mediated signaling, one can tackle immune resistance from multiple angles and remodel the tumor microenvironment to respond to immunotherapies, such as immune checkpoint blockade.

Hypochlorous acid (HOCl), an essential endogenous reactive oxygen species, is integral to various physiological and pathological processes. It is a crucial biomarker linked to inflammation and hepatic damage. The application of near-infrared fluorescence probes for in vivo biological imaging has increased recently, due to their little tissue damage and superior tissue penetration. This paper presents the synthesis of a novel near-infrared fluorescence probe, NS-Id, for the sensitive detection of HOCl. The NS-Id probe exhibits remarkable selectivity, elevated sensitivity (51 nM), and ultrafast response (20 s) to HOCl at an emission wavelength of 591 nm. Furthermore, it has been effectively utilized for visualizing HOCl in both cells and zebrafish. We also proved its capacity to monitor viscosity changes during cell deaths (apoptosis or ferroptosis) at an emission wavelength of 562 nm. These findings underscore the extensive applicability of NS-Id, establishing it as a potential chemical tool for real-time, selective monitoring of HOCl and viscosity.

The convergence of synthetic biology and nanotechnology has created new opportunities for cancer diagnosis and therapy. Engineered microorganisms exhibit unique tumor-targeting, colonization, and immunomodulatory capabilities, while nanomaterials provide versatile platforms for drug delivery, imaging, and controlled therapeutic release. This review summarizes recent advances in the application of engineered microorganisms and nanomaterials in oncology, with a focus on their mechanisms of action, therapeutic potential, and translational challenges. We discuss the roles of the tumor microbiome in cancer progression, microbial engineering strategies for tumor targeting and immune regulation, and the development of nanomaterial-based delivery systems and immunotherapies. Particular attention is given to microbe-nanomaterial hybrid platforms, which combine the advantages of both systems to enhance therapeutic efficacy and modulate the tumor microenvironment. Finally, key challenges related to biosafety, biocompatibility, regulatory approval, and clinical translation are highlighted. The integration of engineered microorganisms and nanomaterials represents a promising strategy for next-generation precision oncology and may accelerate the development of more effective and personalized cancer therapies.

Intranasal drug delivery has emerged as an attractive noninvasive route for local, systemic, and central nervous system (CNS) therapy due to its rapid absorption, avoidance of first-pass metabolism, and potential for nose-to-brain transport. However, the effectiveness of this route is limited by mucociliary clearance, mucus, enzymatic degradation, and poor epithelial permeability. Electrospun fibrous systems have gained increasing attention as intranasal platforms capable of simultaneously addressing these challenges through tailored polymer/excipient selection and formulation design. This review summarizes advances in electrospun intranasal systems and the influence of formulation characteristics on drug-mucosa interactions based on English-language articles identified through PubMed, ScienceDirect, and Google Scholar from January 2010 to May 2026, supplemented by manual reference screening. Mucoadhesive polymers improve drug retention, fast-dissolving polymers promote rapid release and sustained-release polymers prolong drug availability. Particular focus is placed on three complementary mechanisms employed to overcome nasal barriers: mucoadhesion, mucopenetration, and permeation enhancement, which improve nasal retention, mucus transport, epithelial permeation, and biomolecule stability. Recent studies support the potential of electrospun systems for local, systemic, and experimental nose-to-brain delivery, highlighting multifunctional nanofibrous platforms as promising candidates for future intranasal therapies.