Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching

Charalambos Kaittanis, Travis M. Shaffer, Anuja Ogirala, Santimukul Santra, J. Manuel Perez, Gabriela Chiosis, Yueming Li, Lee Josephson and Jan Grimm ()
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Charalambos Kaittanis: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Travis M. Shaffer: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Anuja Ogirala: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Santimukul Santra: Pittsburg State University, 1701 S Broadway Street
J. Manuel Perez: NanoScience Technology Center, University of Central Florida
Gabriela Chiosis: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Yueming Li: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center
Lee Josephson: Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital
Jan Grimm: Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we demonstrate that clinically approved iron oxide nanoparticles (Ferumoxytol) can be utilized to carry one or multiple drugs. These so called ‘nanophores’ retain their cargo within their polymeric coating through weak electrostatic interactions and release it in slightly acidic conditions (pH 6.8 and below). The loading of drugs increases the nanophores’ transverse T2 and longitudinal T1 nuclear magnetic resonance (NMR) proton relaxation times, which is proportional to amount of carried cargo. Chemotherapy with translational nanophores is more effective than the free drug in vitro and in vivo, without subjecting the drugs or the carrier nanoparticle to any chemical modification. Evaluation of cargo incorporation and payload levels in vitro and in vivo can be assessed via benchtop magnetic relaxometers, common NMR instruments or magnetic resonance imaging scanners.

Date: 2014
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DOI: 10.1038/ncomms4384

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