QN-165

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.