Herein, a method for synthesizing and utilizing DNA dendrons to deliver biomolecules to living cells is reported. Inspired by high-density nucleic acid nanostructures, such as spherical nucleic acids, we hypothesized that small clusters of nucleic acids, in the form of DNA dendrons, could be conjugated to biomolecules and facilitate their cellular uptake. We show that DNA dendrons are internalized by 90% of dendritic cells after just 1 h of treatment, with a >20-fold increase in DNA delivery per cell compared with their linear counterparts. This effect is due to the interaction of the DNA dendrons with scavenger receptor-A on cell surfaces, which results in their rapid endocytosis. Moreover, when conjugated to peptides at a single attachment site, dendrons enhance the cellular delivery and activity of both the model ovalbumin 1 peptide and the therapeutically relevant thymosin alpha 1 peptide. These findings show that high-density, multivalent DNA ligands play a significant role in dictating cellular uptake of biomolecules and consequently will expand the scope of deliverable biomolecules to cells. Indeed, DNA dendrons are poised to become agents for the cellular delivery of many molecular and nanoscale materials.
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http://dx.doi.org/10.1021/jacs.1c07240 | DOI Listing |
Neural Regen Res
December 2024
Department of Ophthalmology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mitochondrion
December 2024
Inter-University Centre for Biomedical Research and Super Speciality Hospital, Thalappady, Rubber Board P.O, Kottayam, 686009 Kerala, India. Electronic address:
Mitochondria are the seat of cellular energy and play key roles in regulating several cellular processes such as oxidative phosphorylation, respiration, calcium homeostasis and apoptotic pathways. Mitochondrial dysfunction results in error in oxidative phosphorylation, redox imbalance, mitochondrial DNA mutations, and disturbances in mitochondrial dynamics, all of which can lead to several metabolic and degenerative diseases. A plethora of studies have provided evidence for the involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.
View Article and Find Full Text PDFPharmaceutics
October 2024
A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya, 18, 420008 Kazan, Russia.
Int J Nanomedicine
November 2024
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
Background: Gene therapy is a promising therapeutic approach for treating various disorders by introducing modified nucleic acids to correct cellular dysfunctions or introduce new functions. Despite significant advancements in the field, the effective delivery of nucleic acids remains a challenge, due to biological barriers and the immune system's ability to target and destroy these molecules. Due to their branched structure and ability to condense negatively charged nucleic acids, cationic dendrimers have shown potential in overcoming these challenges.
View Article and Find Full Text PDFBiotechnol J
November 2024
Medical Biotechnology, Life Sciences, TUBITAK Marmara Research Center, Kocaeli, Türkiye.
A promising approach to treat colorectal cancer (CRC) involves combining chemotherapy, epigenetics, and gene therapy to combat drug resistance. Multifunctional nanocarriers have emerged as a valuable tool for targeted CRC therapy. By delivering multiple treatments directly to cancer cells, these nanocarriers offer the potential for improved outcomes and reduced side effects.
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