title: Blurring the Role of Oligonucleotides: Spherical Nucleic Acids as a Drug Delivery Vehicle.
abstract: Nucleic acids are generally regarded as the payload in gene therapy, often requiring a carrier for intracellular delivery. With the recent discovery that spherical nucleic acids enter cells rapidly, we demonstrate that nucleic acids also have the potential to act as a delivery vehicle. Herein, we report an amphiphilic DNA-paclitaxel conjugate, which forms stable micellar nanoparticles in solution. The nucleic acid component acts as both a therapeutic payload for intracellular gene regulation and the delivery vehicle for the drug component. A bioreductively activated, self-immolative disulfide linker is used to tether the drug, allowing free drug to be released upon cell uptake. We found that the DNA-paclitaxel nanostructures enter cells ∼100 times faster than free DNA, exhibit increased stability against nuclease, and show nearly identical cytotoxicity as free drug. These nanostructures allow one to access a gene target and a drug target using only the payloads themselves, bypassing the need for a cocarrier system.
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Xuyu
authors: X
authors: Tan
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Xueguang
authors: X
authors: Lu
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Fei
authors: F
authors: Jia
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Xiaofan
authors: X
authors: Liu
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Yehui
authors: Y
authors: Sun
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Jessica K
authors: JK
authors: Logan
authors: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors: Ke
authors: K
authors: Zhang
mesh_terms: D004247:DNA / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D009841:Oligonucleotides; D004247:DNA; D017239:Paclitaxel