Importantly, modulation of ATP6AP1 expression showed minimal effects on normal breast epithelial cells. Collectively, these findings identify ATP6AP1 as a key downstream mediator of AS1411 and support its potential as a therapeutic target in TNBC.

To address this, we developed a polymer-lipid hybrid nanoparticle functionalized with the AS1411 aptamer, targeting nucleolin to facilitate nucleus-directed delivery...Further evaluation targeting the Lcn2 gene demonstrated higher knockout efficacy and a more potent inhibition of breast cancer cell proliferation. These findings indicate that aptamer-mediated nuclear targeting enhances CRISPR/Cas9 editing efficacy and may offer the potential to advance the performance of non-viral gene therapies.

This study demonstrated that the DNA tetrahedron-based nanocarrier functionalized with AS1411 aptamer effectively delivers vorinostat and enhances its dual action on ferroptosis and EMT in GC. This targeted nanoplatform represents a promising strategy for precise and combinatory GC therapy.

The DNA nanoflowers (Z/H@DFs) are self-assembled from PD-L1 antisense oligonucleotide (ASO), AS1411 G-quadruplex units, Hemin, and ZnPc...The proposed synergistic photo-immunotherapy strategy could realize 3-fold enhancement in tumor infiltrating CD8+ T cells and over 2-fold increase in serum IFN-γ and TNF-α levels. The Z/H@DFMNs patch is a potential solution for melanoma immunome and other skin disorders.

The AS1411 aptamer was embedded at the end of the DNA linker to effectively target nucleolins that are overexpressed in tumor cells...Ultimately, the quantitative relation between MRI signals and local miR-21 concentration was established in vivo. These results indicated the potential of nanoprobes for tumor-related genes diagnosis and quantification, further affirming the possibility of prompt and precise tumor diagnosis.

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.

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.

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.

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.

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.

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.