Theranostic Applications Research Articles

A Systematic Review on the Potential Applications of Theranostic Nanoparticles in Diabetes and its Associated Complication Diabetic Neuropathy

Background: Diabetes neuropathy is a frequent ailment that has a substantial impact on patients by increasing the risk of falls and causing discomfort. The lower extremities are where diabetic neuropathy patients first feel pain. This discomfort could seem like a pinprick, an electric shock, or something else. Objective: Here, we give a comprehensive overview of this quickly developing theranostic appli-cation that includes all relevant imaging, diagnostic, therapeutic, and monitoring elements for the management of diabetes and diabetes neuropathy. Methods: The data for the current study was gathered by searching PubMed and Google Scholar. Several research and review publications from various publishers, including Springer Nature, Bentham Science, PLOS one, MDPI, and ACS Publishing Centre, were evaluated to compile the data. Result: Recent developments in theranostics have shown promise as alternate management ap-proaches for diabetes and ailments linked to diabetes. Numerous nanotechnology-built biosen-sors, including multiwalled carbon nanotubes, copper nanowires, zinc oxide tetrapods, and nano-particle-embedded contact lenses, offer benefits in monitoring diabetic neuropathy. Conclusion: The potency, usability, and dependability of insulin substitutes have been demon-strated by a variety of innovative methods for the management of diabetes, which includes nano-technology approaches using Gene-Based Nanoparticles (siRNA), Liposomes, Exo-somes/Extracellular Vesicles, Neuromodulation, and Inhalable Nanoparticles. Over the past few years, the development of various theranostic nanoparticles for Diabetic neuropathy has experi-enced an unprecedented expansion. Even though much work needs to be done to precisely evalu-ate the genuine benefits provided by these particles, such as issues with nanotoxicity, theranostic nanoparticles will have a significant impact on the field of nanomedicine.

Progress on Carbon Dots with Intrinsic Bioactivities for Multimodal Theranostics.

Carbon dots (CDs) with intrinsic bioactivities are candidates for bioimaging and disease therapy due to their diverse bioactivities, high biocompatibility, and multiple functionalities in multimodal theranostics. It is a multidisciplinary research hotspot that includes biology, physics, materials science, and chemistry. This progress report discusses the CDs with intrinsic bioactivities and their applications in multimodal theranostics. The relationship between the synthesis and structure of CDs is summarized and analyzed from a material and chemical perspective. The bioactivities of CDs including anti-tumor, antibacterial, anti-inflammatory etc. are discussed from biological points of view. Subsequently, the optical and electronic properties of CDs that can be applied in the biomedical field are summarized from a physical perspective. Based on the functional review of CDs, their applications in the biomedical field are reviewed, including optical diagnosis and treatment, biological activity, etc. Unlike previous reviews, this review combines multiple disciplines to gain a more comprehensive understanding of the mechanisms, functions, and applications of CDs with intrinsic bioactivities.

Applications of Novel Microscale and Nanoscale Materials for Theranostics: From Design to Clinical Translation.

The growing global prevalence of chronic diseases has highlighted the limitations of conventional drug delivery methods, which often suffer from non-specific distribution, systemic toxicity, and poor bioavailability. Microscale and nanoscale materials have emerged as innovative solutions, offering enhanced targeting, controlled release, and the convergence of therapeutic and diagnostic functions, referred to as theranostics. This review explores the design principles, mechanisms of action, and clinical applications of various novel micro- and nanomaterials in diseases such as cancer, cardiovascular disorders, and infectious diseases. These materials enable real-time monitoring of therapeutic responses and facilitate precision medicine approaches. Additionally, this paper addresses the significant challenges hindering clinical translation, including biocompatibility, potential toxicity, and regulatory issues. Ongoing clinical trials demonstrate the potential of nanomaterials in theranostic applications, but further research is needed to overcome the barriers to widespread clinical adoption. This work aims to contribute to the acceleration of integrating nanomedicine into clinical practice, ultimately enhancing the efficacy and safety of therapeutic interventions.

Theranostic Applications of Scaffolds in Current Biomedical Research

Theranostic Applications of Scaffolds in Current Biomedical Research

Toward Upconversion (Yb-Er) and near-Infrared (Yb-Ho-Er, Nd-Yb) Thermometry with Sea Urchin Type GdPO4 Nanoarchitectures.

In recent years, optical temperature probes operating in the second near-infrared (BW-II) and third near-infrared (BW-III) biological windows have garnered significant attention in the scientific community. For biological applications these probes offer distinct advantages, including enhanced tissue penetration depth, minimal autofluorescence, and a remarkable improvement in imaging sensitivity and spatial resolution. Moving toward theranostic applications, there is a growing demand for the development of materials that integrate both BW-II and BW-III thermometry systems with drug delivery functionalities. In this study, we concentrate on the development of GdPO4 materials, utilizing both hard and sacrificial template routes to synthesize (hollow) GdPO4 porous sea urchin-like particles. We first investigated the development of a Boltzmann-type thermometer utilizing an Yb-Er upconversion system, designed to operate within the physiological temperature range. Our exploration extends to the potential of GdPO4 particles in near-infrared (NIR) thermometry, spanning the first, second, and third biological windows with systems like Yb-Ho-Er, Nd-Yb, and Ho-Yb, respectively. We further examined the temperature impact of the Yb-Ho-Er system on the NIR emission within a biologically relevant setting, using a phantom that replicates biological tissue. Furthermore, we illustrate the successful loading of these materials with doxorubicin (DOX·HCl), a model anticancer drug, showing these particles exhibit pH-dependent DOX release. This demonstrates the versatility of these materials as upconversion and NIR thermometers while simultaneously serving as an on-demand drug carrier. The investigation involves assessing their cytotoxicity on specific human cells (Normal Human Dermal Fibroblasts (NHDFs)), to determine their viability for potential use in biological applications. The study also investigates how effectively loading the particles with DOX enables targeted delivery to a cellular model of lymphoma (Jurkat E6-1), resulting in cell death. This comprehensive analysis highlights the promising potential of GdPO4 particles for medical applications.

Mitochondria-Targeted Gold Biometallization for Photoacoustically Visualized Photothermal Cancer Therapy.

Subcellular biomineralization systems with cellular intervention functions have shown great potential in cancer theranostic applications. However, the lack of subcellular specificity, high ion concentrations, and long incubation time required for biomineralization still limit its in vivo therapeutic efficacy. Herein, we report a mitochondria-targeted polymer-gold complex (TPPM-Au) to realize mitochondrial biometallization, which involves analogous mechanisms during biomineralization, for cancer treatment in vivo. The TPP-containing TPPM-Au delivered more Au3+ selectively into the mitochondria of cancer cells than normal cells, rapidly mineralizing to gold nanoparticles (GNPs) and consuming a large amount of the antioxidant glutathione (GSH). The formed GNPs can further continue consuming GSH with the atomic economy by forming Au-S with GSH, which further results in the accumulation of reactive oxygen species (ROS), thereby impairing mitochondrial function and inducing cell apoptosis. More importantly, TPPM-Au is capable of having superior tumor-penetrating, excellent photothermal and photoacoustic properties, endowing it with the ability to inhibit tumor growth through spatiotemporally monitorable mitochondria-targeted biometallization and photothermal therapy. The mitochondria-targeted gold biometallization theranostic platform provides insight into the application of subcellularly targeted biometallization or biomineralization in cancer therapy.

Multifunctional gold nanoparticles for cancer theranostics.

The diagnosis and treatment of cancer can often be challenging requiring more attractive options. Some types of cancers are more aggressive than others and symptoms for many cancers are subtle, especially in the early stages. Nanotechnology provides high sensitivity, specificity and multimodal capability for cancer detection, treatment and monitoring. In particular, metal nanoparticles (NPs) such as gold nanoparticles (AuNPs) are attractive nanosystems for researchers interested in bioimaging and therapy. The size, shape and surface of AuNPs can be modified for improving targeting and accumulation in cancer cells, for example through introduction of ligands and surface charge. The interactions of AuNPs with electromagnetic radiation (e.g., visible-near-infrared, X-rays) can be used for photothermal therapy and radiation therapy, through heat generated from light absorption and emission of Auger electrons, respectively. The subsequent expansion and high X-ray attenuation from AuNPs can be used for enhancing contrast for tumor detection (e.g., using photoacoustic, computed tomography imaging). Multi-functionality can be further extended through covalent/non-covalent functionalization, for loading additional imaging/therapeutic molecules for combination therapy and multimodal imaging. In order to cover the important aspects for designing and using AuNPs for cancer theranostics, this review focuses on the synthesis, functionalization and characterization methods that are important for AuNPs, and presents their unique properties and different applications in cancer theranostics.

Novel ultrathin ferrous sulfide nanosheets: Towards replacing black phosphorus in anticancer nanotheranostics

Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H2S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe2+ exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.

Fine-tuning the side-chain length of iridium(III) complexes for enhanced Photophysical properties in Cancer Theranostics

Cyclometalated iridium(III) complexes have emerged as versatile candidates for cancer theranostics, offering integrated diagnostic imaging and potent singlet oxygen (1O2) generation for photodynamic therapy (PDT). However, their application has been limited by subdued photoluminescence, primarily due to intramolecular motion-induced excited energy dissipation. In this study, we address these limitations through the design and synthesis of five novel iridium(III) complexes: IrC2, IrC4, IrC6, IrC8, and IrC12. Our approach employs meticulous side-chain extending strategy to modulate side-chain length, thereby reducing intramolecular motion and significantly enhancing both one- and three-photon emissions and 1O2 production in the aggregated state. Detailed photophysical investigations, supported by crystallographic insights, reveal that side-chain elongation substantially amplifies these properties. Among the synthesized complexes, IrC8 stands out as a superior candidate for image-guided photodynamic therapy in cellular and 3D tumor spheroid models. This investigation pioneers the simultaneous enhancement of dual-photon emissions and PDT efficacy through a novel side-chain extension strategy in iridium(III) complexes, paving the way for their translational application in clinical theranostics.

Dual-Carbon Dots Composite: A Multifunctional Photo-Propelled Nanomotor Against Alzheimer's β-Amyloid.

The abnormal accumulation of β-amyloid protein (Aβ) is considered as the main pathological hallmark of Alzheimer's disease (AD). The design of potent multifunctional theranostic agents targeting Aβ is one of the effective strategies for AD prevention and treatment. Nanomotors as intelligent, advanced, and multifunctional nanoplatforms can perform many complex tasks, but their application in AD theranostics is rare. Herein, sub-10nm multifunctional dual-carbon dots composites (ERCD) with photo-propelled nanomotor behavior are fabricated by conjugating near-infrared (NIR) carbon dots (RCD) of thermogenic and photodynamic capability with the previously reported epigallocatechin gallate-derived carbonized polymer dots (ECD). ERCD-1 (ECD:RCD = 1:2.5) showed potent inhibitory capability similar to ECD in the absence of NIR light, and exhibited photooxygenation activity and nanomotor behavior powered by "self-thermophoretic force" under NIR irradiation, significantly enhancing the inhibition, disaggregation, and photooxygenation capabilities. The nanomotor suppressed Aβ fibrillization and rapidly disaggregated mature Aβ fibrils at very low concentrations (0.5µg mL-1). Moreover, the NIR-activated ERCD-1 imaged Aβ plaques in vivo and prolonged nematode lifespan by 6 d at 2µg mL-1. As a proof-of-concept, this work opened a new avenue to the design of multifunctional sub-10nm nanomotors targeting Aβ for AD theranostics.

Navigating into the Paradigm of Nose-to-brain Delivery of Nanotherapeutics and their Repurposing as Nanotheranostics for Neurodegenerative Diseases.

Repurposing drugs for neurodegenerative diseases using the nose-to-brain route of administration is an intriguing concept with potential benefits. The nose-to-brain route involves delivering drugs directly to the brain via the olfactory or trigeminal pathways, bypassing the blood-brain barrier, which can improve drug efficacy and reduce systemic side effects. Treatment of numerous neurodegenerative diseases such as Multiple sclerosis, Amyotrophic lateral sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases has been attempted using this route of administration. These drugs may include neuroprotective agents, anti-inflammatory drugs, antioxidants, or diseasemodifying therapies. Nanotheranostics, which integrates therapeutic and diagnostic functions in a nanosystem, improves treatment precision and efficacy. Repurposing nanotherapeutics as nanotheranostics for neurodegenerative diseases through the nose-to-brain route of administration holds great potential for both diagnosis and treatment. This review highlights the various mechanisms engaged in transporting nanocarriers from nose-to-brain and the proposed fate of these nanocarriers using different live imaging techniques. Additionally, the discussion covers the recent combinatorial therapeutic approaches and theranostic applications of various nanocarriers used for neurodegenerative diseases through the nose-to-brain. Toxicity to the CNS and nasal mucosa and regulatory considerations about these delivery systems are also deliberated. Overall, repurposed nanoparticles designed as nanotheranostic agents offer a versatile platform for precise diagnosis, targeted therapy, and personalized management of neurodegenerative diseases, holding great promise for improving patient care and advancing our understanding of these complex disorders.

Biomineralization Synthesis of HoMn Nanoparticles for Ultrahigh-Field-Tailored and T1-T2 Dual-Mode MRI-Guided Cancer Theranostics.

Ultrahigh field magnetic resonance imaging (UHF-MRI) (≥7 T) can dramatically boost image resolution and signal-to-noise ratio, which have distinct advantages in multifunctional imaging. However, their research and application are currently limited by the absence of high-field contrast agents (CAs) and the low sensitivity and accuracy of T1/T2 single-modality CAs. Therefore, the development of T1-T2 dual-mode CAs that respond to UHF-MRI and nanoformulations with therapeutic sensitization can bring ideas for the integrated application of precise and synchronous tumor theranostics. Herein, we present a biomimetic mineralization strategy for synthesizing holmium/manganese oxide-bovine serum albumin-photosensitizer chlorin e6 nanohybrids. The hybrid nanoparticles exhibited better tumor accumulation, a suitable time imaging window, and excellent pH-response T1-T2 dual-mode UHF-MRI performance. The antitumor effect comes from the amelioration of the hypoxic tumor microenvironment to promote the synergistic effect of photodynamic therapy and radiotherapy, along with negligible acute toxicity. Undoubtedly, this work not only provides a different perspective for developing multifunctional nanotherapeutics but also promotes the potential clinical exploitation and translation of UHF CAs.

An Overview of Structural Framework and Classification of Theranostic Radiopharmaceuticals

AbstractRadiopharmaceuticals constitute the backbone of nuclear medicine research and have been commonly used in diagnostic imaging and radionuclide therapy. In the past, there has been a strong emphasis on the meticulous design and development of radiotheranostics for targeted molecular imaging and therapy of different types of tumors. Theranostic radiopharmaceuticals offer synergistic advantages of simultaneous molecular imaging and radionuclide therapy all in one molecule. Owing to their successful pre‐clinical and clinical applications, many new theranostic radiopharmaceuticals have been explored in recent years. This review aims to provide a comprehensive overview of the design and the structural framework of theranostic radiopharmaceuticals. In this review, we have primarily focused on the different types of chelating agents, linkers, and radionuclides used for the development of potential radiotheranostics. In addition, this review also summarizes the classification and the different categories of theranostic radiopharmaceuticals such as molecular radiotheranostics and nano‐radiotheranostics along with their pre‐clinical and clinical theranostic applications. The recent developments and the theranostic applications of small molecule‐based radiotheranostics, antibody‐based radiotheranostics, peptide‐based radiotheranostics, and nanoparticle‐based radiotheranostics have also been reviewed for inspiring research efforts towards the development of efficient radiotheranostics.

Multifunctional nanoplatforms based on alumina-coated mesoporous silica with potential for cancer theranostics applications

Multifunctional nanoplatforms based on mesoporous silica coated with alumina were successfully and sustainably synthesized using sodium silicate extracted from rice husk ash (RHA), demonstrating the potential for cancer theranostics. The hybrid nanostructures produced (C2-600 and C4-600), from two different calcination times, exhibited distinct morphologies, textural parameters, and degrees of mesoscopic organization. As expected, the Al2O3 coating on the mesoporous silica nanoparticles (MSNs) reduced the specific surface area from 720 m2/g to 122 m2/g (C2-600) and 57 m2/g (C4-600), while preserving their mesoporous structure. Additionally, both C2-600 and C4-600 showed relatively good stability across a wide pH interval, with a zeta potential of ζ = -15 mV and hydrodynamic diameter (Dh) ranging from 160 to 670 nm, depending on the pH of the medium. These peculiar characteristics resulted in high encapsulation efficiency (EE ≈ 90%) for the doxorubicin (DOX) anticancer drug, as well as sustained drug release in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). Appreciably, C4-600-DOX released approximately 83% of the drug over 96 hours and demonstrated significant biodegradation in simulated biological media. Furthermore, the hybrid nanoplatforms exhibited strong optical absorption between 250 and 420 nm, along with broad and intense photoluminescence (PL) in the near-infrared (NIR) region (680-900 nm), which is highly desirable for NIR-fluorescence diagnostic imaging. Notably, the hybrid nanoplatforms without DOX were non-cytotoxic to fibroblast and Caco-2 cells, while the DOX-loaded nanoplatforms exhibited selectivity and potent anticancer activity, inhibiting approximately 80% of Caco-2 colorectal cancer cells after 72 hours. These findings demonstrate that C2-600 and C4-600 are innovative, multifunctional and biodegradable nanoplatforms with powerful potential as drug carriers and fluorescence imaging agents, making them promising candidates for cancer theranostics.

Nano-theranostics: A novel platform in drug therapy

A fundamental component of customized medicine, theranostics is a therapy approach that combines therapeutics and diagnostics with the goal of increasing drug efficacy and safety while also monitoring treatment response. It will require significant advancements in predictive medicine. Theranostics is linked to tailored drug administration based on test results as well as a diagnostic that screens patients for potential adverse drug reactions. Early diagnosis and treatment have benefited from the designed nanoparticles with unique physicochemical characteristics. This allows treatments to be delivered and the detection method to be employed concurrently, not just before or after treatment but throughout the entire regimen. The development of nanotechnology presents more opportunities for theranostics applications using nanoparticle engineering, and it has demonstrated encouraging outcomes, particularly in cancer therapy when compared with conventional treatments.

Metachronous Second Primary in the Form of Nasopharyngeal Carcinoma Following Treatment of Small Cell Neuroendocrine Carcinoma of the Head and Neck: Dual Tracer PET/CT Findings Highlighting SSTR2 Expression and Its Theranostic Implications

AbstractPatients of head and neck squamous cell carcinoma (HNSCC) experience increased risk of developing second primary cancer (SPC) necessitating active surveillance during their disease course. SPCs are associated with poor prognosis and are the leading cause of long-term morbidity and mortality impacting survival of patients with HNSCC. Small cell neuroendocrine carcinoma (SmNEC) is a rare but aggressive neoplasm with poor prognosis and high risk of local recurrence and distant metastasis. We report an exceedingly rare case of nasopharyngeal carcinoma (NPC) presenting as a recurrence in the form of metachronous second primary to primary SmNEC 9 years after chemotherapy. The dual tracer positron emission tomography and computed tomography (PET/CT) imaging approach ([68Ga]Ga-DOTATATE-PET/CT with 18F-FDG-PET/CT) was explored in such metachronous NPCs, and the findings are illustrated with its potential for theranostic applications. NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

Functionalized PLGA-Based Nanoparticles with Anti-HSV-2 Human Monoclonal Antibody: A Proof of Concept for Early Diagnosis and Targeted Therapy.

Background: Functionalized nanoparticles (NPs) represent a cutting edge in innovative clinical approaches, allowing for the delivery of selected compounds with higher specificity in a wider time frame. They also hold promise for novel theranostic applications that integrate both diagnostic and therapeutic functions. Pathogens are continuously evolving to try to escape the strategies designed to treat them. Objectives: In this work, we describe the development of a biotechnological device, Nano-Immuno-Probes (NIPs), for early detection and infections treatment. Human Herpes Simplex Virus 2 was chosen as model pathogen. Methods: NIPs consist of PLGA-PEG-Sulfone polymeric NPs conjugated to recombinant Fab antibody fragments targeting the viral glycoprotein G2. NIPs synthesis involved multiple steps and was validated through several techniques. Results: DLS analysis indicated an expected size increase with a good polydispersity index. Z-average and z-potential values were measured for PLGA-PEG-Bis-Sulfone NPs (86.6 ± 10.9 nm; -0.7 ± 0.3 mV) and NIPs (151 ± 10.4 nm; -5.1 ± 1.9 mV). SPR assays confirmed NIPs' specificity for the glycoprotein G2, with an apparent KD of 1.03 ± 0.61 µM. NIPs exhibited no cytotoxic effects on VERO cells at 24 and 48 h. Conclusions: This in vitro study showed that NIPs effectively target HSV-2, suggesting the potential use of these nanodevices to deliver both contrast agents as well as therapeutic compounds.

A Promising Therapeutic Strategy of Combining Acoustically Stimulated Nanobubbles and Existing Cancer Treatments.

In recent years, ultrasound-stimulated microbubbles (USMBs) have gained great attention because of their wide theranostic applications. However, due to their micro-size, reaching the targeted site remains a challenge. At present, ultrasound-stimulated nanobubbles (USNBs) have attracted particular interest, and their small size allows them to extravasate easily in the blood vessels penetrating deeper into the tumor vasculature. Incorporating USNBs with existing cancer therapies such as chemotherapy, immunotherapy, and/or radiation therapy in several preclinical models has been demonstrated to have a profound effect on solid tumors. In this review, we provide an understanding of the composition and formation of nanobubbles (NBs), followed by the recent progress of the therapeutic combinatory effect of USNBs and other cancer therapies in cancer treatment.

Engineering two-in-one DNA nanohybrids to evaluate anti-cancer effects through activatable RNA imaging

The development of DNA-based imaging techniques provides a promising way for theranostic applications. However, the dramatic chemical difference between DNA probes and therapeutics significantly hinders the construction of an ideal theranostic system for evaluation of therapeutic effects via in situ molecular imaging. In this work, we report a simple approach for the construction of a two-in-one DNA nanohybrid via one-step assembly of DNA probes and small molecular drugs, enabling evaluation of therapeutic effects via sensitive imaging of apoptosis-related mRNA. The nanohybrid was self-assembled from a rationally designed molecular beacon (MB) probe, doxorubicin (DOX, a chemotherapeutic drug) and Fe (II) ions through coordination interactions, which possesses anti-cancer effects from chemotherapeutics and the capability of efficient co-delivery of DNA probes without transfection agents. By tracking pro-apoptotic Bax mRNA expression with the MB, this system allows real-time monitoring of cell apoptotic process in response to drug treatment, enabling assessment of therapeutic effects of small molecular drugs. In addition, the approach is extended to the imaging of target microRNA in the drug treatment based on flexible DNA probe design, demonstrating the universality of this strategy. Moreover, the modular design of this DNA nanohybrid allows the introduction of photosensitizers into this system for efficient photodynamic therapy and simultaneous mRNA monitoring. This strategy expands the theranostic toolbox for the in situ evaluation of treatment response and screening anticancer drugs.

Targeted imaging of lysosomal zinc ions with a tetrahedral DNA framework fluorescent reporter.

Abnormal levels of zinc ions within endo-lysosomes have been implicated in the progression of Alzheimer's disease (AD), yet the detection of low-concentration zinc ions at the organelle level remains challenging. Here we report the design of an endo-lysosome-targeted fluorescent reporter, Znluorly, for imaging endogenous zinc ions. Znluorly is constructed from an amphiphilic DNA framework (DNF) with programmable size and shape, which can encapsulate zinc-responsive fluorophores within its hydrophobic nanocavity. We find that the tetrahedral DNFs of 20 bp in the edge length are effectively located within endo-lysosomes, which can detect zinc ions with a detection limit of ∼31.9nM (a sensitivity that is ∼2.5 times that of the free fluorophore). Given the organelle-targeting ability and high zinc sensitivity of Znluorly, we employ it to detect endogenous endo-lysosomal zinc ions in neuron cells. We monitor the dynamics of zinc levels in AD model cells and zebrafish, corroborating the positive correlation between zinc levels and AD hallmarks including Aβ aggregates and learning/memory impairments. Our study provides a generalizable strategy for organelle-specific theranostic applications.