DNA nanotechnology in therapeutic modulation and bio-inspired systems for precision medicine

Potentiating In Vivo Precision Cancer Therapy With Modularized Aptamer-Chemotherapeutics Conjugates Based on DNA Tiling-Mediated Structural Nanotechnology.

While DNA origami nanotubes have been often used in the biomedical field, the technical challenges in the assembly at large scale and the susceptibility to degradation limit their exploration for clinical application. In the current contribution, we propose a structural DNA nanotechnology (TMM) for the construction of a degradation-resistant DNA nanotube (DNT) via periodically tiling two structural modules (M) into a modularized (M) tubular DNA nano-architecture. The tube circumference is 118.6 nm, the tube length is 478 nm and the assembly efficiency is almost up to 90%. Upon installation of up-down tumor cell-binding aptamers onto each structural module in a highly precise manner, a protective outer layer was formed. Compared with Biotin-DNA nanowire, the relative nuclease degradation resistance of AS1411-DNT is improved by about 92-fold. Via using commercially synthesized 5-FU-embedded DNA components, we constructed a tumor cell-targeting therapeutic agent-loaded nanoconjugate, AS1411-DNT-5-FU, which exhibits significantly higher therapeutic outcomes than clinic free 5-FU in MCF-7 tumor-bearing mouse models without observable systemic toxicity. While DNA DNT holds great potential for precise drug delivery for cancer therapy, the modularization-based TMM structural DNA nanotechnology is expected to promote the development of next-generation multifunctional 3D-DNA nanostructures and clinical application in precision medicine.

Precision chemical engineering of dendrimers for nucleic acid delivery.

Aptamer-carbon Nanotube Hybrids: Emerging Frontiers in Biomedical Diagnostics and Therapeutics.

Aptamers are single-stranded DNA or RNA molecules that exhibit remarkable affinity and specificity for a broad spectrum of biological targets, positioning them as compelling alternatives to antibodies in both diagnostics and therapeutics. Their ease of synthesis, chemical stability, and tunable binding properties make them highly adaptable for molecular recognition applications. Carbon Nanotubes (CNTs), on the other hand, are renowned for their unique structural, electrical, optical, and mechanical properties, ultimately providing an ideal nanoscale scaffold for aptamer conjugation. When combined with aptamers, CNTs form multifunctional hybrid nanoplatforms that merge the molecular selectivity of aptamers with the high surface area, conductivity, and mechanical strength of CNTs. This review discusses the fundamental concepts, functionalization strategies, and biomedical potential of aptamer-CNT hybrids. Both covalent and non-covalent conjugation approaches are examined, highlighting their impact on stability, sensitivity, and biocompatibility at the biointerface. Recent progress in molecular recognition, biosensing, targeted drug delivery, imaging, and theranostic applications is also summarized. Particular attention is given to the role of CNTs in enhancing electron transfer, signal amplification, and controlled therapeutic release. Moreover, diagnostic and therapeutic applications across various disease models, including cancer, infectious diseases, and neurodegenerative disorders, are highlighted. Furthermore, emerging challenges related to the toxicity, biodegradability, and pharmacokinetics of CNT-based hybrids are addressed, while considering regulatory and ethical perspectives that govern their clinical translation. Overall, aptamer-CNT hybrids hold immense promise as versatile, tunable, and multifunctional platforms that could fundamentally transform next-generation precision medicine and nanotherapeutic systems.

Progress of Framework Nucleic Acids in Tumor Diagnosis and Therapy.

INTRODUCTION Framework Nucleic Acids (FNAs) are precisely self-assembled two- or three-dimensional nucleic acid architectures renowned for their excellent programmability, monodisperse structures, and near-atomic precision. These distinctive properties enable FNAs to function as versatile nanocarriers for targeted biomarker recognition, efficient co-delivery of therapeutics and imaging agents, and stimuli-responsive release within the tumor microenvironment, driving rapid advances in framework nucleic acid-based nanomaterials for tumor theranostics in recent years. METHODS We extensively searched bibliographic databases using keywords such as "framework nucleic acids", "FNA", "DNA nanostructures," and "tumor theranostics". Based on the literature retrieved, we summarized the design and functionalization strategies of FNA-based nanomaterials, reviewed their applications in various tumor therapeutic modalities, and discussed the major challenges for clinical translation. RESULTS FNAs exhibited excellent application prospects across diverse tumor therapeutic modalities. They markedly enhanced targeted drug delivery and therapeutic efficacy in chemotherapy, enabled efficient gene silencing in gene therapy, strengthened antitumor immune responses in immunotherapy, and significantly improved precision in tumor imaging and phototherapy. Collectively, these advantages position FNAs as a highly promising and versatile platform for precision tumor theranostics. DISCUSSION We have further provided a comprehensive discussion of the multifaceted challenges that continue to impede the clinical translation of Framework Nucleic Acid (FNA)-based nanomaterials despite their considerable preclinical promise in tumor theranostics, as well as an in-depth outlook on their future potential in this evolving field. CONCLUSION This review summarizes the remarkable potential of Framework Nucleic Acids (FNAs) as an intelligent nanoplatform for tumor diagnosis and therapy. Nevertheless, several critical challenges persist for clinical translation, including long-term biosafety, scalable manufacturing, and efficient in vivo delivery. Future efforts to address these barriers are expected to accelerate the clinical implementation of FNAs in precision oncology.

Innate Immunity of Framework Nucleic Acids.

ConspectusNucleic acid nanotechnology has fundamentally transcended the classic paradigm of DNA and RNA as passive carriers of genetic blueprints, which enables the rational design and construction of precise nanostructures with defined shapes, dynamics, and functions. This programmability has revolutionized approaches in biomedicine, facilitating breakthroughs in high-resolution molecular diagnostics, spatially and temporally controlled drug delivery, and the creation of synthetic cellular machinery. However, a central challenge for clinical translation is the inherent immunogenicity of nucleic acid materials. Introducing exogenous DNA or RNA nanostructures risks triggering potent innate immune responses, which can lead to rapid clearance, diminished therapeutic efficacy, inflammation, and toxicity. Rather than pursuing universal immunosuppression, researchers are beginning to rationally exploit defined immunostimulatory pathways, which allows for the strategic incorporation of immune-modulatory cues for vaccine development, immunotherapies, and targeted adjuvant systems.In this Account, we review our efforts to develop framework nucleic acids (FNAs) as a platform with modulable innate immunostimulation for biomedical applications in live cells and in vivo. We briefly summarize structural principles of nucleic acid immune recognition mediated by receptors such as toll-like receptors (TLRs) and cyclic GMP-AMP synthase (cGAS). We highlight that such immune recognition is dictated not merely by the abundance of nucleic acids but by key structural parameters, including size, shape, compactness, and the spatial organization of stimulatory nucleic acid motifs. We illustrate strategies to either enhance or suppress immunostimulation through controlled biodistribution, multivalent ligand display, and dynamic structural reconfiguration. These approaches enable tailored applications such as the development of nanovaccines and cancer immunotherapy, or conversely, anti-inflammatory and antioxidant therapies. Looking forward, we envision FNAs as intelligent tools for precision immunomodulation, bridging nanoscale design with immunological outcomes to advance personalized medicine.

Cell-friendly protein based nano-carriers for non-viral gene delivery to cancer cells.

Gene therapy has emerged as one of the most promising approaches in both medical and biotechnological fields due to its capacity to modify, optimize, and regulate target DNA sequences. Recent advancements integrating gene therapy with nanotechnology, particularly through nano-carrier systems, have enabled precise delivery of therapeutic nucleic acids with controlled release at specific pathological sites [1]. Initially focused on monogenic disorders, gene therapy applications have now expanded to a broad spectrum of inherited and acquired diseases [2]. Protein-based nanocarriers have attracted considerable attention as next-generation non-viral vectors due to their intrinsic biocompatibility, biodegradability, and structural versatility [3]. Their ability to encapsulate nucleic acids, support controlled release, and enable targeted delivery makes them attractive candidates for cancer gene therapy. These unique characteristics position protein-based nanocarriers as a cell-friendly and effective strategy for improving the safety and efficiency of gene delivery systems [4]. Consequently, they represent a promising strategy for improving the safety and efficacy of cancer gene therapy. The development of safe, efficient, and biocompatible vectors remains a critical determinant of therapeutic success. Recombinant peptides, despite their therapeutic potential, face challenges such as high toxicity, instability, poor bioavailability, and costly production, which gene therapy strategies aim to overcome [5]. Techniques including gene knockdown, mutation correction, and gene insertion are central to modern gene therapy approaches. This article reviews the recent progress and challenges associated with nano-based non-viral vectors designed for targeted delivery of DNA into cancerous cells.