J. Nanotheranostics, Volume 7, Issue 3 (September 2026) – 5 articles

Hydrogel-forming microneedles (HFMNs) are minimally invasive interfaces that access interstitial fluid (ISF) through skin penetration, swelling-mediated uptake, analyte diffusion, and hydrated sensor integration. This review examines HFMN architectures, skin–device interfaces, ISF transport, molecular-recognition and signal-transduction strategies, analytical performance, benchmarking, wear-associated failure modes, therapeutic monitoring, and translational priorities. The field has expanded from glucose sensing to metabolites, ions, hormones, proteins, nucleic acids, microbial and wound biomarkers, and therapeutic drugs, enabled by advances in hydrogel chemistry, conductive networks, nanostructured electrodes, catalysis, affinity recognition, molecular imprinting, optical readouts, and multiplexed wearables. Performance remains context dependent and requires physiological range, calibration stability, biofouling resistance, reliable insertion, validated ISF-reference correlations, and interpretable thresholds. Evidence is strongest in artificial matrices, ex vivo tissue, and animals, while human validation remains limited. Translation will require standardized mechanics and transport reporting, longer wear studies, sterilization-compatible chemistries, scalable manufacturing, and clinical validation. HFMNs may complement rather than replace blood-based diagnostics. Full article

Theranostic nanoparticles, which integrate diagnostic imaging and therapeutic delivery within a single nanoplatform, represent a transformative paradigm in oncological nanomedicine. Despite substantial preclinical progress, the field faces persistent gaps in rational nanoparticle design informed by tumor biology, preclinical model fidelity, and clinical translation. This review critically synthesizes theranostic nanoparticle research across three underexplored domains. First, we examine tumor microenvironment features—reactive oxygen species dynamics, glutathione gradients, hypoxia, and proteasomal dysregulation—as mechanistic drivers of nanoparticle responsiveness. Second, we evaluate redox-responsive and proteasome-targeted nanoplatforms that exploit these cues for stimuli-triggered drug release and simultaneous imaging readout. Third, we address the unmet need for three-dimensional organoid and microfluidic tumor models as predictive preclinical testing environments, given the well-documented limitations of conventional two-dimensional cultures. Cancer subtype-specific applications are discussed for breast cancer, HPV-associated malignancies, colorectal cancer, and prostate cancer. Clinical translation barriers—including pharmacokinetic constraints, protein corona formation, immune clearance, anti-PEG antibodies, complement activation-related pseudoallergy, and FDA/EMA regulatory pathways—are addressed from a clinical oncology perspective. The review concludes with a research roadmap integrating proteomics-guided nanoparticle engineering, patient-derived organoid biobanks, and artificial intelligence-assisted design as priority areas for next-generation oncological theranostics. Full article

Cancer diagnosis and longitudinal monitoring increasingly depend on biosensing technologies capable of detecting low-abundance, heterogeneous, and dynamic biomarkers in complex biological samples. Hydrogel-based biosensors offer a distinctive materials platform for this purpose because their hydrated, porous, tunable, and biomolecule-compatible networks can integrate molecular recognition, antifouling protection, nanomaterial-assisted signal amplification, and three-dimensional biological interfaces within a single sensing architecture. Across cancer-focused applications, hydrogels have been engineered to detect nucleic acids, soluble protein markers, tumor-associated enzymes, extracellular vesicles, circulating tumor cells, metabolic products, redox signals, and tumor microenvironmental cues in matrices such as serum, plasma, saliva, urine, sweat, blood, cell lysates, and three-dimensional cancer models. Their functional value extends beyond passive immobilization: hydrogels can serve as programmable recognition networks, gated reservoirs, conductive interfaces, optical and plasmonic scaffolds, degradable enzyme-responsive matrices, and cell-compatible microenvironments. These attributes support sensitive biomarker detection, multiplexed profiling, portable and smartphone-assisted formats, wearable or minimally invasive systems, and dynamic monitoring of tumor behavior and treatment response. Nevertheless, the field remains uneven in translational maturity, with many platforms still requiring broader clinical validation, standardized benchmarking, manufacturable device designs, reproducible fabrication, and practical assessment of assay complexity, storage stability, and patient-sample performance. This review positions biomarker-responsive hydrogels as a convergence point between advanced materials engineering and clinically oriented cancer biosensing, with particular promise for liquid biopsy, decentralized diagnostics, and tumor-state-resolved monitoring. Full article

Asthma is a prevalent, long-term inflammatory airway condition that is difficult to diagnose and treat because there is no single reliable diagnostic test. Misdiagnosis is therefore common, with rates as high as 73% in juvenile groups and up to 35% in adult populations. This ultimately exacerbates their illness by postponing therapy for some people and administering needless medication to others. Although well-known biomarkers such as blood eosinophils and fractional exhaled nitric oxide, as well as conventional diagnostic techniques such as spirometry, have improved clinical assessment, they are nevertheless constrained in many healthcare settings by limited availability, high cost, and inconsistent use. Furthermore, these indicators primarily reflect type-2 inflammation and are less useful for non-type-2 asthma, highlighting the need for more comprehensive, readily accessible diagnostic techniques. Identifying novel biomarkers of oxidative stress, metabolic alterations, and airway inflammation, including volatile organic compounds and redox-related chemicals, has been the focus of recent studies. These biomarkers offer opportunities for improved disease phenotyping and non-invasive detection. Simultaneously, advances in biosensor technology have enabled highly sensitive platforms to rapidly detect these biomarkers at low concentrations. In particular, optical biosensors are becoming more and more popular due to their ability to do real-time detection without the need for labels and their ease of miniaturization for point-of-care devices. This work summarizes traditional diagnostic tools alongside existing information on asthma phenotypes and clinically important biomarkers, and discusses advanced biosensors ranging from electrochemical to optical systems, including recent developments in nanomaterial-enhanced optical biosensing techniques. The importance of artificial intelligence and smartphone-integrated hardware is also covered, along with the main challenges that need to be overcome for these technologies to become useful clinical tools for asthma diagnosis and monitoring. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article