DataVXAdvanced Functional MaterialsPaper
journal article·2025-05Open access

Engineering Novel DNA Nanoarchitectures for Targeted Drug Delivery and Aptamer Mediated Apoptosis in Cancer Therapeutics

Abhisek Dwivedy, Dhyanesh Baskaran, Gaurav Sharma, Wei Hong, Dhanush Gandavadi, Abhichart Krissanaprasit, Joonsu Han, Yusheng Liu, Zack Zimmers, Tshepo Mafokwane, Ichrak Hayah, Neha Chauhan, Mengxi Zheng, Sherwood Yao, Keith Fraser, John S. Decker, Xiaohe Jin, Hua Wang, Adam D. Friedman, Xing Wang

Advanced Functional Materials· Volume 35· Issue 22
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Source abstract

Abstract

Abstract The specific and potent delivery of anticancer drugs to targeted cancer stem cells (CSCs) remains a critical need to maximize on‐target, on‐tumor effects while minimizing on‐target, off‐tumor toxicities. Herein, the designer DNA architecture (DDA)‐templated drug conjugates (DDA‐DCs) customized are presented to deliver daunorubicin (Dau) specifically and potently to a subset of CSCs: acute myeloid leukemia (AML) leukemic stem cells (LSCs) that often maintain minimal residual disease (MRD) and cause relapse. These DDA‐DCs target LSCs via CD117‐ and CD123‐binding aptamers: aptamers that when used alone disrupts the MAP Kinase and apoptosis signaling pathways, leading to a 40% reduction in cell viability over 72 h. These aptamers, when loaded with dsDNA‐intercalating Dau and docked to DDA platforms, exhibit potent and selective cytotoxicity against CD117+/CD123+ AML cells, achieving a reduction in effective drug dosage by 500‐fold ex vivo and up to 10‐fold in vivo AML models. These DDA‐DC strategy confers many advantages over other targeted therapies, such as selective cell targeting based on cell surface biomarker profiles (not just individual biomarkers that are often expressed by healthy tissues), titratable affinity, pattern matching, multiplexing, multidrug delivery, and target cell drug sensitization. The combination of these features yields superior anticancer efficacies with minimal off‐target effects.
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Research context

Nanomaterials

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · DNA and Nucleic Acid Chemistry

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Bioengineering Grainger College of Engineering University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Holonyak Micro & Nanotechnology Lab Grainger College of Engineering University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Department of Materials Science and Engineering Grainger College of Engineering University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Atom Bioworks Inc. Cary NC 27513 USA

Carl R. Woese Institute for Genomic Biology University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Department of Chemistry University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Department of Life and Consumer Sciences College of Agriculture and Environmental Sciences University of South Africa, Science Campus, Florida Johannesburg South Africa

Faculty of Sciences Center for Plant and Microbial Biotechnology College of Agriculture and Environmental Sciences Biodiversity and Environment, Mohammed V University Rabat Morocco

Department of Biological Sciences Rensselaer Polytechnic Institute Troy NY 12180 USA

Cancer Center at Illinois Urbana IL 61801 USA

Carle College of Medicine University of Illinois at Urbana‐Champaign Urbana IL 61801 USA

Funding

National Institute of Biomedical Imaging and Bioengineering · National Science Foundation

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