QN-165

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.

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.

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.

Herein, we report a cucurbit[7]uril (CB[7])-mediated upconversion nanoplatform co-loaded with AS1411-C15/Hemin (AH) and the photosensitizer triphenylporphyrin derivative (TPP)...This further activates TPP to transform O2 into singlet oxygen (1O2), effectively promoting cancer cell apoptosis. Experimental results demonstrate that this multifunctional upconversion nanoplatform provides an effective strategy for targeted photodynamic drug delivery.

Here, we report an artificial metalloDNAzyme (Ru-ac@TDF) by incorporating acridine-conjugated ruthenium complexes (Ru-ac) into a tetrahedral DNA framework (TDF) functionalized with the AS1411 aptamer for enhanced bioorthogonal prodrug activation. Following nucleolin-mediated selective uptake by cancer cells, Ru-ac@TDF efficiently catalyzes intracellular activation of an alloc-caged doxorubicin prodrug, producing pronounced antiproliferative effect in vitro and potent tumor suppression in vivo, with enhanced intratumoral drug exposure and minimal systemic toxicity. Overall, this work establishes programmable DNA nanostructures as architecturally defined platform for organizing TMCs with high density and spatial precision, providing a conceptually new route toward enhanced bioorthogonal catalysis.

Functionalization with the AS1411 aptamer enables tumor targeting, while conjugation with the KLA peptide facilitates mitochondrial localization, achieving spatiotemporal codelivery of both miRNAs and sorafenib. In vivo, Sor@AKAExo exhibits potent antitumor efficacy with excellent biosafety. This work presents a bioinspired plant-derived exosome-based immunotherapy that synergistically activates both ferroptosis and apoptosis circuits with precise spatiotemporal control, addressing the obstacles of absent active targeting, limited drug delivery efficacy, and adaptive drug resistance in TNBC treatment.

Overall, the high targeting ability of AS1411 and the multifunctionality of albumin could enhance ERN efficacy against EC, inhibit the proliferation of EC cells, and induce ferroptosis. AS1411-BSA@ERN nanoparticles may be a targeted ferroptosis inducer, providing a potential strategy for targeted treatment against EC.

The nanosystem was constructed by assembling gold nanotriangles functionalized with an MMP-2-cleavable Cy5 peptide and the tumor-targeting aptamer AS1411, with PDA-coated AA-[Zn(OH)4]2- nanoparticles via NH2-PEG-SH linkers...This activatable nanosystem is a versatile platform for real-time imaging and synergistic therapy. It is a promising tool for precision intervention in breast cancer bone metastasis.

Through analysis of representative clinical programs, including the systemic nucleolin-targeting aptamer AS1411, the microenvironment-modulating CXCL12 inhibitor NOX-A12, and the locally administered personalized platform AM003, this review highlights how delivery strategy, target context, and clinical deployment critically shape therapeutic outcomes. Recurrent translational barriers related to systemic exposure, tumor accessibility, regulatory pathways, and competition with established modalities are identified, together with lessons from both failed and emerging programs. Finally, we discuss practical strategies to improve clinical alignment, including human-relevant selection models, localized or combination therapies, and AI-assisted design, positioning aptamers for context-appropriate roles in future precision oncology.

These PROTACs induced NCL- and MDM2-dependent ubiquitination and degradation of VEGFR2 or EGFR in GBM cells, demonstrating potent anti-tumour activity. Collectively, our findings identify EV-transferred NCL as a key mediator of BTB formation and a functional transcytosis receptor for AS1411, providing a promising strategy for developing BTB-permeable, targeted therapy for GBM.

Although most aptamer-based checkpoint inhibitors remain in preclinical stages, early phase clinical investigations (primarily with C-X-C motif chemokine ligand 12 (CXCL12)-targeting Spiegelmer NOX-A12 in combination settings, as well as earlier programs such as AS1411 targeting nucleolin) have demonstrated effective inhibition of immune checkpoint signaling, reactivation of T-cell function, and synergistic effects when combined with existing immunotherapies. Preclinical and early phase clinical investigations have demonstrated that aptamers can effectively inhibit immune checkpoint signaling, reactivate T-cell function, and potentiate synergistic effects when combined with existing immunotherapies. By critically evaluating current progress and identifying key translational challenges, this review provides strategic insights into the future development of aptamer-based immunotherapeutic platforms, ultimately guiding the advancement of more precise, cost-effective, and personalized cancer treatment modalities.

Herein, a cross-shaped DNA skeleton was rationally engineered by leveraging programmable DNA assembly and AS1411 aptamer-mediated tumor targeting to achieve specific activation of the cGAS-STING pathway...In vitro and in vivo evaluations further validated that the DNA scaffold not only triggered innate immune activation but also inhibited tumor progression in TNBC models. Overall, this work provides a promising strategy for the development of safe and effective TNBC immunotherapy.