QN-165 / Qualigen Therap, University of Louisville, Advanced Cancer Therap - LARVOL DELTA

A Layered-Responsive DNA Tetrahedral Nanomachine for Precise Cancer Cell Imaging and Selective cGAS-STING Signaling Activation. (PubMed, Anal Chem) - "Through AS1411 aptamer modification, DTDN achieved selective targeting and efficient cancer cell internalization...Furthermore, the generated long nicked dsDNA not only provided an amplified fluorescence signal for cancer cell imaging but also acted as potent cGAS activators, thereby triggering the cGAS-STING pathway. Hence, this work provides a programmable, safe, and reliable nucleic acid nanoplatform for cancer diagnosis and cGAS-STING pathway-based regulatory therapy."

Journal • Oncology • MIR21

Rational redesign of high-activity G-quadruplex DNAzyme through flanking and looping of nucleobases. (PubMed, Sci Rep) - "Remarkably, the modified B730 variants retained activity at elevated H₂O₂ concentrations (4.25 mM), achieving up to 8-fold catalytic enhancement and outperforming high-activity DNAzymes including AS1411 and CatG4. These redesigned DNAzymes demonstrated improved peroxidase activity and resistance to oxidative inactivation, addressing a major limitation of both natural and artificial peroxidases. Our findings establish flanking and loop engineering as a cost-effective and broadly applicable strategy for optimizing G4 DNAzymes and underscore their potential in the development of next-generation biosensors."

Journal

Design and evaluation of dual-functional aptamer-peptide conjugates as a platform for targeted cancer therapy. (PubMed, Eur J Pharm Sci) - "AS1411 is a G-rich DNA aptamer that exhibits intrinsic antitumor activity through selective binding to nucleolin, a protein overexpressed in many cancers...One conjugate displayed an enhanced antiproliferative effect compared to the unconjugated components, underscoring the therapeutic potential of this modular design. Overall, this work demonstrates the potential of aptamer-peptide conjugates as a promising strategy for next-generation targeted cancer therapeutics, combining targeted delivery with synergistic therapeutic effects."

Journal • Breast Cancer • Oncology • Solid Tumor • NCL

Dual Aptamers-Based SETDB1 PROTACs as Effective Anti-Tumor Strategies for Breast Cancer. (PubMed, Adv Sci (Weinh)) - "This aptamer was conjugated to the nucleolin-targeting aptamer AS1411, generating a single-strand PROTAC (AP-SETDB1-S6A) and a partial double-strand PROTAC (AP-SETDB1-D2), both of which exhibit good serum stability...Functional assays demonstrated that both AP-SETDB1-S6A and AP-SETDB1-D2 significantly inhibit breast cancer cell proliferation and migration, and resensitize drug-resistant breast cancer cells to tamoxifen. Notably, they further enhance the cytotoxic activity of CD8+ T cells against breast cancer cells and directly target breast cancer cells to suppress tumor growth in vivo. This study establishes dual aptamers-based PROTACs targeting SETDB1, offering effective therapeutic strategies for breast cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD8 • NCL • SETDB1

Synthesis and Evaluation of AS1411-Lenalidomide-Targeted Degradation Chimera in Antitumor Therapy. (PubMed, Pharmaceuticals (Basel)) - " This study provides compelling evidence demonstrating that C4 is a highly promising anticancer compound. It also provides important evidence for the development of novel nucleic acid aptamer-PROTAC conjugate drugs for more clinical applications."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • NCL

Redirecting Tryptophan Metabolism Through Host-Microbial Crosstalk to Enhance Precise Bioorthogonal Chemoimmunotherapy. (PubMed, Adv Mater) - "To tackle these issues, here we fabricate a bioorthogonal probiotic nanosystem (NP@ZIF-8@Apt-Lr) by engineering prodrug catalysts and an indoleamine 2,3-dioxygenase (IDO) inhibitor onto AS1411 aptamer-modified Lactobacillus reuteri (Lr)...Furthermore, it significantly enhances the efficacy of chemoimmunotherapy by suppressing bilateral tumor development and inducing an immune memory response. This work presents a new strategy for enhancing bioorthogonal chemoimmunotherapy through precise prodrug activation and probiotic-mediated metabolic reprogramming by host-microbial crosstalk."

Journal • Oncology

In vivo dynamic monitoring of self-assembled melatonin nanodrug combined with photothermal effects to alleviate hypoxia to attenuate tumor aggressiveness. (PubMed, J Nanobiotechnology) - "Ultimately, the findings from both in vitro and in vivo experiments demonstrated that the simultaneous use of MLT and PTT could effectively suppress hypoxia in tumors and trigger programmed apoptosis. As a result, this approach holds promise as a potential combined therapeutic option with enhanced therapeutic effects."

Journal • Preclinical • Oncology • HIF1A

Aptamer-engineered NIR-II Ru-doped carbon quantum dot nanozyme for photoacoustic imaging-guided synergistic photothermal and catalytic cancer therapy. (PubMed, J Nanobiotechnology) - "Both in vitro and in vivo studies demonstrate that Ru-CQDs-AS1411@PEG enable precise photoacoustic tumor imaging and potent tumor ablation under NIR-II laser irradiation via synergistic photothermal and catalytic reactive oxygen species (ROS) generation. This work provides a green-engineered, aptamer-guided CQD nanozyme platform with integrated targeting, imaging, and therapeutic functionalities, offering a promising and sustainable approach for precision cancer theranostics."

Journal • Oncology

Universal Microfluidic Platform for Multifunctional Surface Modification of Small Extracellular Vesicles. (PubMed, J Extracell Vesicles) - "Functionally, RGE peptide-modified sEVs exhibited a 54.13% increase in transmembrane transport efficiency in the in vitro model and enhanced infiltration into glioma spheroid, while AS1411 aptamer-conjugated sEVs showed 77.8% targeting specificity towards breast cancer cells, compared to 32.5% for normal breast cells...Unlike traditional donor-cell-dependent genetic modification approaches, ExoSE enables universal, scalable modification of sEVs from diverse sources, including highly abundant milk-derived sEVs, and accommodates diverse ligand types such as peptides, aptamers and proteins. This device represents a transformative advancement in sEV engineering, establishing a standardized and scalable framework for precision-targeted sEV therapeutics with enhanced clinical potential."

Journal • Brain Cancer • Breast Cancer • Glioma • Oncology • Solid Tumor

Dual-Mode Aptamer AP1-F Achieves Molecular-Morphological Precision in Cancer Diagnostics via Membrane NCL Targeting. (PubMed, Curr Issues Mol Biol) - "By means of rigorous optimization, AP1-F attained a greater than ten-fold fluorescence signal ratio between malignant and normal cells in co-cultures, exceeding the extensively researched AS1411...This combination biochemical-morphological approach accomplished subtype differentiation with a single-step, non-permeabilized process that maintained lower cytotoxicity and tissue integrity. AP1-F enhances diagnostic accuracy by utilizing spatial confinement to eradicate intracellular interference, connecting molecular specificity to intraoperative margin evaluation or biopsy categorization."

Journal • Oncology • NCL

A dual-enzyme-like nanozyme adjuvant alleviates tumor hypoxia to enhance photothermally ferroptosis-immune synergistic tumor therapy. (PubMed, Mater Today Bio) - "Herein, we developed a dual-enzyme-like nanozyme adjuvant (Mn3O4&MLT@PDA-AS1411, MMPA) through the integration of Mn3O4 nanozyme and melatonin (MLT) using polydopamine, which alleviates tumor hypoxia to enhance photothermally augmented ferroptosis-immune synergistic therapy...In vivo studies demonstrate that this strategy effectively alleviates tumor hypoxia, resulting in the complete suppression of distant tumors in a metastatic model. This approach also first explores the promotion of ferroptosis and immune activation of MLT, providing an innovative strategy for multi-mechanism synergistic treatment."

Journal • Immune Modulation • Immunology • Oncology • HIF1A

Enhancing the intracellular delivery of antisense oligonucleotides (ASO) : a comparative study of aptamer, vitamin E, and cholesterol ASO conjugates. (PubMed, RSC Adv) - "The ASO PNAT524 was conjugated to two DNA aptamers-AS1411 and S2.2-via thiol and triethylene glycol (TEG) linkers, respectively...These findings indicate that aptamer conjugation provides minimal benefit for ASO delivery, while cholesterol and vitamin E conjugation significantly enhance intracellular delivery and therapeutic activity. The 524-Chol conjugate holds strong potential for adaptation in ASOs targeting EGFR and other oncogenes, representing a promising avenue for ASO-based cancer therapeutics."

Journal • Oncology • EGFR

Nucleolin perturbation alters membrane lipid homeostasis. (PubMed, Mol Omics) - "Ratiometric imaging of Di-4-ANEPPS-labeled cells showed that AS1411 decreases the fluidity of intracellular membranes. Thus, aptamer engagement of nucleolin affects lipid biosynthesis and homeostasis, likely contributing to its roles in cell size control."

Journal • Oncology • NCL

A dual-multivalent aptamer-DNA nanocarriers for enhancing antitumor effects of photodynamic-chemotherapy combined therapy. (PubMed, Colloids Surf B Biointerfaces) - "AMH-Ncas had an RCA scaffold with repeats units, which can self-assemble with the functional complementary chains of AS1411 aptamers, MUC1 aptamers and hypoxia inducible factor 1α (HIF-1α) antisense DNA. The thermodynamic data of the binding of photosensitizer new methylene blue N (NMBN) and chemotherapeutic drug doxorubicin (DOX) to AMH-Ncas indicated that AMH-Ncas had higher drug loading capacity and the first loading of NMBN was more favorable...AMH-Ncas + NMBN + DOX system exhibited excellent synergistic anti-tumor effects. This study provides a theoretical basis for the co-delivery of combined drugs by DNA nanocarriers to achieve enhanced PDT-chemotherapy synergistic therapy."

Journal • Oncology • HIF1A • MUC1

In Situ PROTAC Synthesis Enabled by Pathologically Activated Bioorthogonal Catalysis for Precision Cancer Therapy. (PubMed, J Am Chem Soc) - "These components are encapsulated within AS1411 aptamer-conjugated liposomes to enhance cellular uptake and systemic delivery...The modularity of the ABC-PROTAC strategy is demonstrated by utilizing diverse warheads, including small molecules and DNA motifs, to degrade BRD4, PARP1, and NF-κB. Together, this strategy establishes a precise method for targeted protein degradation while minimizing the systemic toxicity associated with conventional PROTACs."

Journal • Oncology • Targeted Protein Degradation • BRD4 • NCL • PARP1

Nanoscale mapping of nucleolin-aptamer interactions on lung cancer cells reveals binding affinity hierarchy and spatial heterogeneity. (PubMed, Anal Methods) - "This study localized nucleolin on lung cancer and normal cells at single-molecule resolution using the single molecule recognition imaging mode of Atomic Force Microscopy (AFM) with three aptamers: 9FU-AS1411, AS1411, and CRO...This work pioneers high-resolution spatial mapping of nucleolin-aptamer interactions, offering novel methodologies for studying protein-aptamer binding kinetics and electrical properties at unprecedented precision (0.1 mV resolution). The approaches established here not only advance nucleolin-targeted cancer therapy but also provide a framework for investigating other protein-aptamer systems in biomedical research."

Heterogeneity • Journal • Lung Cancer • Oncology • Solid Tumor • NCL

Nucleolin-Targeted DNA Nanoflowers Enable Multimodal Synergistic Cancer Therapy. (PubMed, Biomater Res) - "AS1411 aptamer, coded in the long single-stranded DNA sequence, provided GCD with tumor-targeting ability, enhancing its bio-safety...We also examined immune cell death induction and the immune regulation role of GCD and found that the combination of anti-programmed death-1 antibody further enhanced its antitumor effect. These results contribute to the further study and application of copper-based drug development."

Journal • Oncology • NCL

Shattering kinetic constraints: hierarchically activatable DNAzyme nanoantennas for in situ mRNA imaging and precise cancer theranostics. (PubMed, Biosens Bioelectron) - "Once encountering cancer cells, hairpin 1 (H1) recognizes the nucleolin via an aptamer AS1411, and meanwhile the i-motif in H1 undergoes structure switching at extracellular acid pH, enabling the cross-opening of H2, H3, H4, H5 for in situ self-assembly of two-sided DNAzyme nanoantennas...It can profile Egr-1 mRNA level in diverse human cells, and distinguish Egr-1 mRNA level in breast cancer tissues and healthy counterparts. Moreover, it can be applied for high-contrast imaging of Egr-1 mRNA in vivo, efficient gene silencing, and enhanced tumor ablation, with promising applications in smart gene therapeutics and precise nanomedicines."

Journal • Breast Cancer • Gene Therapies • Oncology • Solid Tumor • NCL

AS1411 Aptamer-Conjugated Liposomal siRNA Targeting MTA2 Suppresses PI3K/AKT Signaling in Pancreatic Cancer Cells. (PubMed, Int J Mol Sci) - "Treatment of MIA PaCa-2 cells with AS1411-Lipm[siRNA] significantly reduced MTA2 expression by ~60%, substantially restored PTEN, and inhibited AKT phosphorylation by ~50%, leading to decreased cell viability, impaired migration by ~75%, and increased apoptosis by ~35%, while sparing nucleolin-negative cells. These findings highlight AS1411-Lipm[siRNA] as a promising platform for selective siRNA delivery and potent molecular inhibition in PDAC therapy."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MTA2 • NCL • PTEN

An aptamer-conjugated mesoporous polydopamine formulation for synergistic targeted and photothermal therapy of hepatocellular carcinoma. (PubMed, Int J Pharm X) - "This study aimed to create multifunctional nanoparticles (NPs), specifically AS1411@MPDA-Len-Cy5.5 (AMLC), for the purpose of developing effective strategies for treating hepatocellular carcinoma (HCC) through targeted therapy and photothermal therapy (PTT). The study demonstrates that AMLC, a multifunctional nano-delivery system, significantly enhances Lenvatinib's tumor-targeting capacity while exhibiting excellent biocompatibility. Combined with photothermal therapy (PTT), it demonstrates potent antitumor efficacy, showing promising clinical translation potential for hepatocellular carcinoma (HCC) therapy."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Au-CuS Hierarchical Self-Assembled Multimodal Diagnosis and Treatment Platform for the Synergistic Treatment of Melanoma. (PubMed, Langmuir) - "To further enhance the targeting ability of AuNRs-D12-CuS, we modified the surface with the AS1411 aptamer to achieve specific recognition of overexpressed nucleolin on the surface of B16. In addition, doxorubicin (DOX) was effectively incorporated into the AuNRs-D12-CuS, forming a multifunctional nanosystem with chemotherapeutic function (AuNRs-D12-CuS@DOX), and its drug encapsulation efficiency reached approximately 64%...In vitro experimental results showed that after labeling the prepared composite nanomaterials with nucleic acid red dye (NA-red), the material exhibited excellent fluorescence imaging performance when coincubated with cells for 30 min. In addition, under low-dose conditions, its killing efficiency against B16 cells could reach 50%, which was significantly superior to single-drug treatment or simple photothermal therapy."

Journal • Melanoma • Oncology • Solid Tumor • DNA2 • NCL

Neutrophil-Inspired Film for Nonadhesive Capture of Tumor Cells through Synergistic Functionalization of Zwitterions and Aptamers. (PubMed, Chem Bio Eng) - "Then, amino-modified aptamer (NH2-AS1411) targeting tumor cells, mimicking the β-integrin on neutrophil membranes, was further grafted onto hydrolyzed PAN surface to obtain the AS/PScG/PU-PAN film. The resulting AS/PScG/PU-PAN film demonstrates excellent specific capture ability of tumor cells, while maintaining the morphology of tumor cells, providing a promising solution for cancer therapy."

Journal • Oncology • VCAM1

Computational simulations of RNA-based aptamers targeting EpCAM+ breast cancer cells (ACS-Fall 2025) - "Based on these analyses, aptamer AS1411 was selected as the most appropriate candidate for EpCAM-mediated breast cancer cell detection. This work advances the potential of EpCAM-targeted aptamers as targeted therapeutic and diagnostic agents against breast cancer."

Breast Cancer • Oncology • Solid Tumor • EPCAM

Sonodynamic Therapy-Based DNA Nanocarriers with Hypoxia-Inducible Factor-1α Silencing Activation for Precision Lung Cancer Therapy. (PubMed, Biomater Res) - "In this study, manganese-containing DNA nanoflowers (DHA-DDF) loaded with doxorubicin (DOX) were functionalized with an AS1411 aptamer and a hypoxia-inducible factor-1α (HIF-1α) antisense sequence...The programmable, biocompatible, and multifunctional nanoflowers demonstrate a notable improvement in the efficacy of SDT and provide robust tumor inhibition in both cellular and animal models. The findings highlight the potential of DNA nanotechnology in advancing innovative cancer therapies."

Journal • Lung Cancer • Oncology • Solid Tumor • HIF1A

AS1411 aptamer in melanoma therapy: Harnessing targeted strategies for precision treatment. (PubMed, Pathol Res Pract) - "Additionally, AS1411-conjugated therapies, including peptide and siRNA constructs, show potential in disrupting tumor vasculature and silencing cancer-related genes. Overall, AS1411-modified nanoparticles represent a transformative approach in skin cancer therapy, warranting further clinical investigation."

Journal • Review • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • NCL