Microfluidic-generated Lipid-graphene Oxide Nanoparticles for Gene Delivery


Authors: R. Di Santo, E. Quagliarini, S. Palchetti, D. Pozzi, V. Palmieri, G. Perini, M. Papi, A.L. Capriotti, A. Laganà, and G. Caracciolo

Journal: Applied Physics Letter

DOI: 10.1063/1.5100932

Publication - Abstract

June 11, 2019

Abstract

Graphene oxide (GO) is employed in a broad range of biomedical applications including antimicrobial therapies, scaffolds for tissue engineering, and drug delivery, among others. However, the inability to load it efficiently with double-stranded DNA impairs its use as a gene delivery system. To overcome this limitation, in this work, the functionalization of GO with cationic lipids (CL) is proficiently accomplished by microfluidic manufacturing. To this end, we use CLs 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and {3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]} cholesterol (DC-Chol) and zwitterionic dioleoylphosphatidylethanolamine and cholesterol to generate a library of 9 CL formulations with systematic changes in lipid composition. Combined dynamic light scattering, microelectrophoresis, and atomic force microscopy reveal that graphene oxide/cationic lipid (GOCL) nanoparticles (NPs) are positively charged and uniformly coated by one lipid bilayer. GOCL NPs are able to condense plasmid DNA into stable, nanosized complexes whose size and zeta-potential can be finely tuned by adjusting the DNA/GOCL weight ratio, Rw. Luciferase assay results show that positively charged GOCL/DNA complexes (Rw = 0.2) efficiently transfect HeLa cells with no appreciable cytotoxicity. In particular, the ternary GOCL formulation made of DOTAP, DC-Chol, and Cholesterol (GOCL8) is as efficient as Lipofectamine® 3000 in transfecting cells, but much less cytotoxic. Confocal microscopy clarifies that the high transfection efficiency of GOCL8 is due to its massive cellular uptake and cytosolic DNA release. Implications for nonviral gene delivery applications are discussed.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Over the last two decades, liquid perfluorocarbon nanodroplets (PFC-NDs), also known as Phase Change Contrast Agents (PCCAs), that are capable of vaporizing into gaseous echogenic microbubbles via an external stimulus, have gained much attention for diagnostic and therapeutic app...
Read More


Publication - Abstract

The approval of two mRNA vaccines as urgent prophylactic treatments against Covid-19 made them a realistic alternative to conventional vaccination methods. However, naked mRNA is rapidly degraded by the body and cannot effectively penetrate cells. Vectors capable of addressing th...
Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.