QN-165 / AIxCrypto Holdings, University of Louisville, Advanced Cancer Therapeutics - LARVOL DELTA

Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives. (PubMed, AAPS J) - "Furthermore, functionalizing the surface with targeting ligands, such as MUC1 aptamers, AS1411, or iRGD peptides, can further increase its specificity for CRC cells. Advances in drug delivery techniques, including passive incubation, electroporation, and chemical modification, have enabled the incorporation of conventional chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and SN-38, as well as nucleic acid-based therapies, including microRNA and siRNA. Due to the limitations and invasive nature of current treatments for CRC, new studies to obtain innovative and targeted therapeutic strategies are essential to reduce harmful effects. Therefore, exosome-based drug delivery systems represent a promising and clinically relevant avenue for future cancer therapy."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • MUC1

A tumor-targeting strategy based on covalent aptamer-carborane conjugates. (PubMed, Bioorg Chem) - "Confocal microscopy further confirmed preferential localization of AS1411-CB conjugates on the surface of MCF-7 cells, consistent with nucleolin-mediated targeting. These results demonstrated that AS1411-CB conjugates preserved the targeting capability of AS1411 and highlighted its potential as a boron delivery platform for tumor-targeting applications."

Journal • Breast Cancer • Oncology • Solid Tumor • NCL

A photoregulated DNA nanoflower for spatiotemporally controlled monitoring of adenosine triphosphate in living cells. (PubMed, Anal Chim Acta) - "The TAPE integrates three core functional modules: the AS1411 aptamer module for tumor cell targeting via nucleolin binding, a cholesterol-modified module for enhanced membrane interaction and delivery, and a photocontrollable ATP-sensing module. In cellular experiments, TAPE enabled the spatiotemporally controlled imaging of intracellular ATP, successfully monitoring ATP level fluctuations induced by pharmacological agents etoposide under photocleavage-mediated activation. In conclusion, this study develops a spatiotemporally controlled intracellular ATP imaging strategy, offering a reliable platform for tumor research."

Journal • Oncology • NCL

Aptamer-Functionalized DNA Frameworks as Targeted Drug Buffers for Concentration Regulation of Maytansine. (PubMed, ACS Appl Bio Mater) - "Both of the buffers integrate nucleolin-targeting aptamer (Apt-AS1411) for cancer cell recognition and DM1-specific aptamer (Apt-Seq2-X) for regulating DM1 concentration within a desired therapeutic range...Notably, even as CDM1 varied from 50 to 1000 nM, A-MTP-3S2 still maintained free DM1 at a relatively constant level (1-55 nM), confirming its great buffering capacity. Our work offers a facile strategy for simultaneous targeted delivery and precise concentration regulation of low-specific and high-toxic drugs."

Journal • Oncology • NCL

Inhaled Tumor-Responsive Mos2 Nanoflowers Enhance Locoregional Therapy in Orthotopic Lung Cancer (IASLC-WCLC 2026) - "Methods : Metallic-phase MoS2 nanoflowers were synthesized and sequentially modified with dendrigraft poly-L-lysine, doxorubicin, and AS1411 aptamer...Conclusions : In an orthotopic lung cancer model, inhaled Apt@DGL-MoS2/DOX improved intrapulmonary tumor delivery, enhanced antitumor efficacy, and reduced systemic toxicity signals compared with conventional delivery patterns. These findings support inhalation-based, tumor-responsive chemo-chemodynamic therapy as a clinically relevant locoregional treatment strategy for lung-dominant malignancies and provide a strong preclinical rationale for further translational development."

Lung Cancer • Oncology • Solid Tumor

Tetrahedral DNA-guided catalytic hairpin assembly for reference-calibrated intracellular microRNA imaging and sensing. (PubMed, Analyst) - "We report a tetrahedral DNA platform that positions a catalytic hairpin assembly within an optimal spatial confinement window, thereby maximizing target-triggered amplification relative to background leakage. AS1411-mediated targeting and a β-actin reference channel further enable selective, internally calibrated imaging and sensing of intracellular microRNA-21."

Journal • MIR21

Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis. (PubMed, Adv Sci (Weinh)) - "To translate this mechanistic insight, we develop an FLS-targeted proteolysis-targeting chimera (PROTAC) by conjugating the OGT inhibitor OSMI-1 to the AS1411 aptamer, which selectively binds surface nucleolin (NCL) overexpressed on pathogenic FLSs and, upon internalization, employs NCL as a molecular bridge to recruit the E3 ligase MDM2 for cell-selective OGT degradation. This PROTAC suppresses FLS pathogenicity, attenuates arthritis in mice, and demonstrates additive therapeutic benefit when combined with the TNF-α inhibitor etanercept. Collectively, our work establishes a translational paradigm that progresses from AI-driven target discovery and mechanistic elucidation to the rational design of a cell-type-specific degradation therapy, offering a strategy to overcome the stromal-driven therapeutic barrier in RA."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • BTG2 • NCL

AS1411-Induced Lipidomic Alterations and Therapeutic Insights in U-87 Glioblastoma Cells. (PubMed, Biomolecules) - "While AS1411 subjects cancer cells to methuotic vacuolization stress, it simultaneously reduces internal structural membrane fluidity and renders the cells metabolically vulnerable to ferroptosis. In conclusion, these detailed lipidomic results indicate that AS1411 treatment proceeds strictly through targeted remodeling and an adaptive scaffolding response."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • NCL

CD-73 blocking black phosphorus nanosheets hitchhiked on erythrocytes via affinity difference of AS1411 aptamer for targeted photothermal-immunotherapy of lung cancer. (PubMed, Mater Today Bio) - "The combined PTT and CD-73 blockade reshapes the immunosuppressive microenvironment and boosts potential antitumor immunity, significantly suppresses lung cancer growth. This RBC-based delivery strategy facilitates targeted nanomedicine accumulation and robust antitumor immune activation, providing an effective platform for lung cancer suppression."

Journal • Lung Cancer • Oncology • Solid Tumor • CD73 • CD8 • NCL

High-Sensitivity Magnetic Particle Spectroscopy Platform for Precise, Specific, and Rapid Detection of Infectious Disease and Cancer-Related Biomarkers. (PubMed, ACS Meas Sci Au) - "Single-core SHP-25 MNPs were conjugated with recombinant human angiotensin-converting enzyme 2 (ACE2) protein, antinucleoprotein (anti_NP) antibodies, and AS1411 aptamer to target the SARS-CoV-2 receptor-binding domain (RBD), influenza A hemagglutinin type-1, neuraminidase type-1 (H1N1) nucleoprotein, and breast cancer biomarker nucleolin, respectively...Comparative analysis shows that monoclonal antibody-conjugated MNPs provide greater specificity and quantitative robustness in MPS measurements than polyclonal antibodies. The high sensitivity of the developed MPS, combined with the superior specificity of monoclonal antibodies, enables precise biosensing with potential clinical relevance."

Biomarker • Journal • Breast Cancer • Infectious Disease • Influenza • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • NCL

A cell surface-targeted MNAzyme-aptamer system for highly sensitive and visual detection of cancer cells via nucleolin activation. (PubMed, Anal Chim Acta) - "Upon target recognition, the AS1411 aptamer undergoes a conformational change from its duplex state to specifically bind nucleolin, which is overexpressed on tumor cell surfaces...The system exploits stable membrane anchoring coupled with a target-activated "switch" mechanism, thereby minimizing false positives from nonspecific binding. This strategy significantly enhances detection efficiency and accuracy while accommodating both high-sensitivity instrumental analysis and low-cost visual screening, offering a promising approach to advance cancer diagnostics."

Journal • Oncology • NCL

Targeted therapy of colon cancer with aptamer-functionalized albumin nanoparticles loaded with disulfiram. (PubMed, Nanotechnology) - "To overcome these limitations, we developed a novel targeted drug delivery system (Apt-NPs-DSF) by encapsulating disulfiram (DSF) within albumin nanoparticles (NPs) functionalized with the nucleolin-targeting AS1411 aptamer. Importantly, in vivo study confirmed that Apt-NPs-DSF achieved superior antitumor efficacy without raising systemic toxicity, outperforming non-targeted counterparts. Collectively, these results suggest that Apt-NPs-DSF has potential in the targeted treatment of colon cancer."

Journal • Colon Cancer • Colorectal Cancer • Developmental Disorders • Oncology • Solid Tumor • NCL

Potentiating In Vivo Precision Cancer Therapy With Modularized Aptamer-Chemotherapeutics Conjugates Based on DNA Tiling-Mediated Structural Nanotechnology. (PubMed, Small) - "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."

Journal • Preclinical • Oncology

Ultrasound-guided spatial delivery based on acoustic bacteria to enhance cancer immunotherapy. (PubMed, Int J Pharm) - "AAB were genetically engineered to express gas vesicles (GVs) for enhanced ultrasound contrast and surface-modified with AS1411 aptamer via amide condensation to promote tumor accumulation...This enhanced therapeutic effect was mediated by preserved availability of functional CD47 targets on viable tumor cells, coupled with robust induction of M1 macrophage polarization and a potent pro-inflammatory immune microenvironment within the tumor. This study provides a practical image-guided strategy to overcome the therapeutic barriers imposed by intratumoral heterogeneity and maximize the efficacy of bacterial cancer immunotherapy."

Journal • Oncology

AS1411-functionalized albumin nanoparticles for nucleolin-targeted realgar delivery and therapy in triple-negative breast cancer. (PubMed, Front Pharmacol) - "In addition, the formulation showed good in vivo tolerability, with no evident systemic toxicity or hemolytic activity. These findings indicate that AS1411-functionalized albumin NPs are a promising delivery system for improving the antitumor efficacy and safety profile of realgar in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • GADD45G • NCL

Rational Design of pH-Switches Based on Mismatch-Guided Hybridization of I-Motifs and G-Quadruplexes. (PubMed, Anal Chem) - "Using the AS1411 aptamer to nucleolin as a model G-quadruplex, we designed 19 pH-switches having a transition pH from 5.2 to 7.4 to validate our framework. Ultimately, we derived empirically grounded guidelines for the engineering of the pH-switches and thermodynamic approaches to predict their properties analytically."

Journal • NCL

Synergistic magnetic nano-chemotherapy overcomes chemoresistance in 3D breast cancer models. (PubMed, Mikrochim Acta) - "Additionally, m-PEG-coated IONCs were functionalized with doxorubicin (DOX) and the tumor-targeting aptamer AS1411 to enable targeted magneto-chemotherapy (MCT) in 3D breast cancer models. The results show that magneto-chemotherapy (MCT) reduces cancer cell viability to 76.41% in 2D cultures and 77.27% in 3D cultures, highlighting the potential of 3D models for enhancing the effectiveness of targeted therapies in breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Development of AS1411 Aptamer-Targeted Solid Lipid Nanoparticles to Improve Anticancer Efficiency of Lawsone. (PubMed, Adv Pharm Bull) - "Targeted nanoparticles displayed higher cellular uptake and cytotoxicity in nucleolin-positive cells (C26 cells) compared to nucleolin-negative cells (CHO cells), with no substantial differences observed. These results illustrated that LWS-SLN-Chit-Apt could be considered as a great candidate for further studies and in vivo trials."

Journal • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • NCL

A triangular split-DNAzyme scaffold for high-contrast microRNA imaging in living cells. (PubMed, Biosens Bioelectron) - "Functionalized with a Cy3-BHQ2 pair and an AS1411 aptamer for targeted, carrier-free cellular delivery, the TDPzyme achieved an approximately 18-fold enhancement in sensitivity over conventional closed-arm designs, establishing a linear range of 0.1 nM to 40.0 nM and a limit of detection of 50.3 pM (3σ). Furthermore, time-lapse dynamic imaging demonstrated that the TDPzyme enables highly reliable, high-contrast discrimination of miR-21 expression between tumor and normal cells. Ultimately, the TDPzyme design offers a robust, structurally controllable platform for developing highly sensitive, low-background biosensors applicable to demanding live-cell imaging and precision molecular diagnostics."

Journal • Oncology • MIR21

Dual-Mechanism Aptamer-Drug Complex Overcomes Paclitaxel Resistance in Ovarian Cancer via Structural Constraint and Telomerase Inhibition. (PubMed, Research (Wash D C)) - "To overcome these challenges, we engineered PSaA360, a structurally constrained aptamer-drug conjugate with a dual-functional molecular lock that simultaneously rigidifies the AS1411 aptamer and delivers potent telomerase inhibition. In vivo, PSaA360 exhibited marked tumor inhibition with minimal systemic toxicity. By transforming a therapeutic agent into a structural stabilizer, PSaA360 establishes a new paradigm for mechanism-guided aptamer engineering in chemotherapy-resistant malignancies."

Journal • Platinum resistant • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • NCL

COF@DNAzyme Empowering Endogenous Copper for One-Stitch Bioorthogonal Catalysis-Based Anticancer Therapy. (PubMed, Angew Chem Int Ed Engl) - "By integrating the DNAzyme CLICK-17 and the tumor-targeting aptamer AS1411 onto covalent organic framework (COF) nanoparticles, co-delivery of both the catalyst and the prodrugs in a single nanoplatform (COF-P@C-A) is achieved...CLICK-17 then efficiently catalyzes the CuAAC reaction for localized drug synthesis, maximizing therapeutic efficacy and minimizing off-target effects. This strategy offers a safe, synchronized, and clinically translatable approach to bioorthogonal prodrug activation."

Journal • Oncology

Ultrasound-synergized targeted nanoparticles suppress proliferation, migration and invasion of hypoxic lung cancer cells in vitro (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "AS1411-D/C-MPDA nanoparticles combined with ultrasound allow targeted delivery of anticancer drugs and represent a promising strategy for synergistic treatment of lung cancer by integrating physical acoustics, pharmaceutical chemistry, and tumor microenvironment regulation."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • ANXA5 • CAT

Aptamer-Functionalized Liposome Delivery System Based on Multifunctional Microreactor Design. (PubMed, ACS Appl Mater Interfaces) - "Through computational fluid dynamics (CFD) simulations, we optimized the flow-rate ratio (lipid phase/aqueous phase/postprocessing phase = 1:5:2) and achieved AS1411 aptamer modification via thiol-maleimide chemistry...In vitro and in vivo studies confirmed the nanoparticles' superior stability and tumor-targeting specificity. This modular microreactor offers exceptional flexibility in tailoring liposome properties for breast cancer therapy and demonstrates scalability for industrial production through dimensional or parallel amplification."

Journal • Breast Cancer • Oncology • Solid Tumor

Targeted therapy of highly aggressive thyroid papillary carcinoma by AS1411-guided nanomaterials. (PubMed, Nanomedicine (Lond)) - "Combined chemo-photothermal therapy significantly suppressed tumor growth in vivo with no obvious systemic toxicity, and the antitumor effect was associated with regulation of mitochondrial apoptosis-related genes. This multifunctional targeted nanoplatform exerts potent synergistic antitumor efficacy against aggressive PTC with good biosafety, providing a promising novel therapeutic strategy for radioiodine-refractory PTC."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • NCL

AS1411 aptamer-functionalized, cell membrane-camouflaged nanoparticles for targeted tumor cells imaging in the Raman silent region. (PubMed, Anal Bioanal Chem) - "As a result, they were successfully used for SERS imaging of tissue sections, allowing high-contrast delineation of tumor tissue margins with results consistent with hematoxylin and eosin (H&E) staining. Collectively, these findings demonstrate that our work holds significant promise for background-free tumor visualization."

Journal • Oncology • NCL