DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. DNA nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, and structural versatility, making them ideal candidates for advanced drug delivery, organelle regulation, and cellular function modulation. This Perspective explores the emerging role of DNs in modulating cellular behavior through organelle-targeted interventions. We highlight current advances in nuclear, mitochondrial, and lysosomal targeting, showcasing applications ranging from gene delivery to cancer therapeutics. For instance, DNs have enabled precision mitochondrial disruption in cancer cells, lysosomal pH modulation to enhance gene silencing, and nuclear delivery of gene-editing templates. While DNs hold immense promise for advancing nanomedicine, outstanding challenges include optimizing biological interactions and addressing safety concerns. This Perspective highlights the current potential of DNs for rational control of targeted organelles, which could lead to novel therapeutic strategies and advancement of precision nanomedicines in the future.

• Publication type
• Journal Article MeSH
• Review MeSH

The folding and export of proteins and hydrolysis of unfolded proteins are disbalanced in the endoplasmic reticulum (ER) of cancer cells, leading to so-called ER stress. Agents further augmenting this effect are used as anticancer drugs including clinically approved proteasome inhibitors bortezomib and carfilzomib. However, these drugs can affect normal cells, which also rely strongly on ER functions, leading, for example, to accumulation of reactive oxygen species (ROS). To address this problem, we have developed ER-targeted prodrugs activated only in cancer cells in the presence of elevated ROS amounts. These compounds are conjugates of cholic acid with N-alkylaminoferrocene-based prodrugs. We confirmed their accumulation in the ER of cancer cells, their anticancer efficacy, and cancer cell specificity. These prodrugs induce ER stress, attenuate mitochondrial membrane potential, and generate mitochondrial ROS leading to cell death via necrosis. We also demonstrated that the new prodrugs are activated in vivo in Nemeth-Kellner lymphoma (NK/Ly) murine model.

• Keywords
• aminoferrocene, cancer, endoplasmic reticulum, prodrugs, reactive oxygen species,
• MeSH
• Endoplasmic Reticulum drug effects   metabolism   MeSH
• Neoplasms, Experimental drug therapy   metabolism   MeSH
• Humans MeSH
• Lymphoma drug therapy   metabolism   MeSH
• Molecular Structure MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Prodrugs chemistry   pharmacology   MeSH
• Antineoplastic Agents chemistry   pharmacology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Prodrugs MeSH
• Antineoplastic Agents MeSH
• Reactive Oxygen Species MeSH