title: Superparamagnetic iron oxide-encapsulating polymersome nanocarriers for biofilm eradication.
abstract: The rising prevalence and severity of antibiotic-resistant biofilm infections poses an alarming threat to public health worldwide. Here, biocompatible multi-compartment nanocarriers were synthesized to contain both hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and the hydrophilic antibiotic methicillin for the treatment of medical device-associated infections. SPION co-encapsulation was found to confer unique properties, enhancing both nanocarrier relaxivity and magneticity compared to individual SPIONs. These iron oxide-encapsulating polymersomes (IOPs) penetrated 20 μm thick Staphylococcus epidermidis biofilms with high efficiency following the application of an external magnetic field. Three-dimensional laser scanning confocal microscopy revealed differential bacteria death as a function of drug and SPION loading. Complete eradication of all bacteria throughout the biofilm thickness was achieved using an optimized IOP formulation containing 40 μg/mL SPION and 20 μg/mL of methicillin. Importantly, this formulation was selectively toxic towards methicillin-resistant biofilm cells but not towards mammalian cells. These novel iron oxide-encapsulating polymersomes demonstrate that it is possible to overcome antibiotic-resistant biofilms by controlling the positioning of nanocarriers containing two or more therapeutics.
authors.affiliation: Department of Bioengineering, Northeastern University, Boston, MA 02115, USA; Nanomedicine Science and Technology Center, Northeastern University, Boston, MA 02115, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Geilich
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.
authors.forename: Ilia
authors.initials: I
authors.lastname: Gelfat
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, MA 02115, USA; Department of Physics, Northeastern University, Boston, MA 02115, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, MA 02115, USA; Department of Physics, Northeastern University, Boston, MA 02115, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: van de Ven
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: th.webster@northeastern.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013242:Sterilization / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D003911:Dextrans; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D011108:Polymers; C097921:ferumoxtran-10
keywords: Antibiotic-resistance; Biofilm; Nanomedicine; Polymersome; SPION; Staphylococcus epidermidis