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Article Enhanced Doxorubicin Cytotoxicity on Breast Cancer Spheroids by Aptamer Targeted Co-Delivery With Hyaluronidase(Wiley, 2025) Kavruk, Murat; Demirel, Dide Su; Bonyadi, Farzaneh; Guner, Buket Cakmak; Dursun, Ali Dogan; Vakifahmetoglu, Cekdar; Ozalp, Veli CengizBreast cancer is one of the most prevalent solid tumors in women and can be classified into subtypes based on molecular characteristics, such as hormone receptor status and HER2 expression. Aptamers, highly specific affinity molecules, are extensively studied for targeted drug delivery using nanocarriers to enhance anti-cancer efficacy. This study focused on HER2-responsive co-delivery of doxorubicin and hyaluronidase via aptamer-gated mesoporous silica nanoparticles to improve therapeutic outcomes in solid tumors. SK-BR-3 spheroids are employed as a model for resistant tumor environments in solid tumors. Previous research is shown that conjugating cytotoxic drugs with nanoparticles or cells enhances drug penetration into tumor spheroids. In this work, doxorubicin is loaded into mesoporous silica nanoparticles and capped with HER2-specific aptamers, while the particle surface is functionalized with hyaluronidase. This dual-functionalized nanocarrier system achieves an approximate to 8.5-fold increase in cytotoxicity compared to aptamer-targeted delivery lacking hyaluronidase. The enhanced effect is attributed to hyaluronidase-mediated loosening of the spheroid structure, facilitating nanoparticle penetration and localized release of doxorubicin at high concentrations on HER2-positive cells.Review Citation - WoS: 28Citation - Scopus: 22Enhanced Selex Platforms for Aptamer Selection With Improved Characteristics: a Review(Springernature, 2024) Didarian, Reza; Ozbek, Hatice K.; Ozalp, Veli C.; Erel, Ozcan; Yildirim-Tirgil, NimetThis review delves into the advancements in molecular recognition through enhanced SELEX (Systematic Evolution of Ligands by Exponential Enrichment) platforms and post-aptamer modifications. Aptamers, with their superior specificity and affinity compared to antibodies, are central to this discussion. Despite the advantages of the SELEX process-encompassing stages like ssDNA library preparation, incubation, separation, and PCR amplification-it faces challenges, such as nuclease susceptibility. To address these issues and propel aptamer technology forward, we examine next-generation SELEX platforms, including microfluidic-based SELEX, capillary electrophoresis SELEX, cell-based aptamer selection, counter-SELEX, in vivo SELEX, and high-throughput sequencing SELEX, highlighting their respective merits and innovations. Furthermore, this article underscores the significance of post-aptamer modifications, particularly chemical strategies that enhance aptamer stability, reduce renal filtration, and expand their target range, thereby broadening their utility in diagnostics, therapeutics, and nanotechnology. By synthesizing these advanced SELEX platforms and modifications, this review illuminates the dynamic progress in aptamer research and outlines the ongoing efforts to surmount existing challenges and enhance their clinical applicability, charting a path for future breakthroughs in this evolving field.
