title: Synthesis and Assembly of Click-Nucleic-Acid-Containing PEG-PLGA Nanoparticles for DNA Delivery.
abstract: Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Harguindey
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Dylan W
authors.initials: DW
authors.lastname: Domaille
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Fairbanks
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.|Materials Science and Engineering Program, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Bowman
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.|Materials Science and Engineering Program, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Cha
mesh_terms: D004247:DNA; D004337:Drug Carriers; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D004247:DNA
keywords: CNA; DNA; PLGA; delivery vehicles; polymer nanoparticles