J. Nanotheranostics, Volume 7, Issue 2 (June 2026) – 7 articles

DNA methylation is a key mechanism in epigenetic regulation and plays a pivotal role in tumor initiation, progression, and therapeutic resistance. We begin by elucidating how the dysregulation of key DNA methylation enzymes in tumors drives concurrent global hypomethylation and cytosine-phosphate-guanine (CpG) island hypermethylation. This aberrant epigenetic landscape promotes tumorigenesis through silencing tumor suppressor genes and triggering abnormal activation of oncogenic signaling pathways. Notably, DNA methylation is intimately linked to cellular pyroptosis. In particular, the hypermethylation-mediated silencing of pyroptosis effector genes represents a critical epigenetic mechanism underlying acquired drug resistance. Targeting DNA methylation with epigenetic drugs offers a novel strategy to resensitize tumors to chemotherapy, radiotherapy, and immunotherapy. Moreover, advances in nanomedicine have yielded smart platforms for the precise administration of epigenetic modulators and combination therapies. These platforms enable a coordinated “epigenetic priming-pyroptosis execution” strategy, which holds promises for reversing therapeutic resistance and remodeling the tumor immune microenvironment. By integrating DNA methylation regulation, pyroptosis mechanisms, and nano-targeted strategies, this review aims to provide a theoretical framework and novel perspectives for developing innovative, epigenetically driven anti-tumor therapies. Full article

Nanomaterial-based biosensors have advanced analytical methodologies by enhancing signal transduction, interfacial reactivity, and molecular recognition across diverse sensing platforms. In parallel, the diversity of nanomaterial compositions, architectures, and interfacial designs has expanded the range of available sensing strategies and performance outcomes. This review addresses limitations through a structure–property–function framework that links nanomaterial characteristics to sensing behavior, performance determinants, and application-specific requirements. Within this framework, nanomaterials are classified according to their dominant functional roles in biosensing, including plasmonic, electroactive, fluorescent and quantum-confined, porous, and hybrid architectures. The influence of morphology, surface chemistry, conductivity, and interfacial design on electrochemical, optical, and hybrid transduction mechanisms is critically examined, and key performance parameters, including sensitivity, selectivity, limit of detection, response time, stability, and reproducibility, are discussed in relation to material properties and sensing configuration. Recent advances in clinical biomarker detection, pathogen and nucleic acid analysis, and environmental and food safety monitoring are also evaluated to illustrate how nanomaterial design is tailored to different analytical contexts. Current limitations related to reproducibility, interface engineering, long-term stability, and scalable device integration are highlighted, together with future directions for the rational development of robust and application-oriented biosensor platforms. Full article

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

Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, controlled release, targeted delivery, and diagnostic performance, thereby enabling theranostic applications. This review evaluates major nanoparticle platforms in therapy and diagnosis, comparing their mechanisms, applications, and challenges while highlighting their potential to advance precision medicine and theranostic strategies. Method: For providing the context and evidence, relevant literatures were sourced from Google Scholar, PubMed, and ScienceDirect using targeted keywords including “drug delivery,” “diagnostics,” “nanoparticles,” “nanomedicine,” “nano drug delivery,” “nanotheranostics,” “targeted therapy,” “controlled drug release,” “solid lipid nanoparticles (SLNs),” “lipid nano carriers (LNCs),” and “inorganic nanoparticles.” Although no strict time limit was applied during the literature search, clinical trial data were collected and analyzed up to January 2026. Given that clinical trial registries are continuously updated, the included trials represent the status at the time of data retrieval. However, it is pertinent to note that the earliest relevant studies appeared in 1973. Conclusions: This review highlights nanoparticle fundamentals, major material classes, mechanisms of action, and applications in targeted therapy, imaging, and theranostics. It also addresses translational barriers related to safety, scalability, biological complexity, and regulatory compliance. Overcoming these challenges through standardized characterization and interdisciplinary collaboration is crucial for clinical adoption. Future efforts should focus on AI-driven design, computational tools, smart nanomedicines, and advanced biosensing technologies to integrate nanoparticle-enabled precision diagnostics and therapy into routine clinical practice. Full article

Nanotheranostic platforms integrating diagnostic and therapeutic functions within a single system have attracted significant attention in precision medicine. However, conventional nanotheranostics based on systemic administration often suffer from off-target accumulation, limited retention at disease sites, and dose-limiting toxicity. To address these limitations, hydrogel-integrated nanotheranostic systems have emerged as a promising strategy for achieving localized diagnosis and therapy with improved spatial control and safety. This review provides a comprehensive overview of recent advances in hydrogel–nanomaterial nanotheranostic platforms, focusing on their design principles, diagnostic capabilities, and therapeutic applications. We discuss the complementary roles of hydrogels and nanomaterials, where hydrogels function as localized reservoirs and tissue interfaces, and nanomaterials provide imaging and therapeutic functionalities. Key integration strategies including physical encapsulation, chemical conjugation, and in situ nanoparticle formation are systematically compared. We further summarize localized diagnostic modalities such as real-time imaging and therapy monitoring, and highlight research-driven applications in cancer treatment, inflammation and infection management, and tissue regeneration. Finally, major translational challenges and future perspectives toward personalized, image-guided local theranostics are discussed. Overall, hydrogel-based nanotheranostic platforms represent a versatile approach for next-generation localized precision medicine. Full article

Personalized medicine aims to tailor therapy based on patient-specific molecular and biological characteristics, while nanomedicine focuses on engineering delivery systems to overcome pharmacokinetic and biological barriers. Despite major advances, both fields are limited when applied separately. This review discusses integrating patient stratification with rational nanocarrier design, a combination termed personalized nanomedicine, as a framework to maximize therapeutic index. With emphasis on clinically validated and late-stage examples, we analyze how molecular stratification informs therapeutic design, with particular focus on translational constraints and engineering trade-offs. Results: Personalized medicine enables precise target identification and patient stratification but does not address delivery barriers that limit therapeutic distribution and safety. Conversely, nanomedicine overcomes delivery challenges but exhibits patient- and disease-dependent variability. Merging these approaches allows nanocarrier design to be tailored to disease biology and patient-specific barriers to effective treatment. Recent clinically successful examples demonstrate that co-optimizing biological targeting and delivery engineering can improve translational robustness. Conclusions: Personalized nanomedicine represents a convergence of molecular stratification and engineered delivery systems, a fusion that facilitates context-dependent therapeutic design rather than one-size-fits-all formulations. While significant translational and regulatory challenges remain, treating delivery design as an integral component of personalization offers a viable path toward broader clinical implementation. Continuing to integrate patient profiling with nanoengineering principles will be essential for translating personalized nanomedicine from promising case studies into standard clinical practice. Full article

Glioblastoma (GBM) remains among the most treatment-refractory human malignancies. It is characterized by profound radioresistance and a highly immunosuppressive tumor microenvironment, limiting the durable efficacy of radiotherapy. Beyond direct cytotoxicity, ionizing radiation can induce immunogenic cell death and the release of damage-associated molecular patterns (DAMPs), including surface-exposed calreticulin, HMGB1, extracellular ATP/adenosine, and tumor-derived DNA. These signals engage pattern-recognition receptors and cGAS–STING–type I interferon pathways, transiently promoting antigen presentation and immune activation. In GBM, however, DAMP signaling frequently evolves toward chronic inflammation and immune suppression, characterized by myeloid cell recruitment, adenosine accumulation, and immune checkpoint upregulation, thereby contributing to tumor regrowth and radioresistance. This dual immune-regulatory role of DAMPs highlights the importance of temporal and contextual interpretation of radiation-induced immune responses. In this review, we summarize current mechanistic and translational evidence on DAMP-mediated immunomodulation in GBM radiotherapy; discuss modality-dependent considerations across photon, proton, and high-LET irradiation; and evaluate the emerging potential of DAMPs as dynamic biomarkers of treatment response. We further outline how integration of DAMP profiling with liquid biopsy, imaging, and nanotheranostic platforms may support biologically informed and adaptive radiotherapy strategies for glioblastoma. Full article