4.8 Article

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

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NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4384

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资金

  1. Department of Defense Prostate Cancer Research Program of the Congressionally Directed Medical Research Programs [W81XWH-12-1-0509]
  2. Louis V. Gerstner Young Investigator Award
  3. Starr Cancer Consortium [I4-A427]
  4. MSKCC Experimental Therapeutics Center
  5. Alex's Lemonade Stand Foundation
  6. NIH [P30 CA008748-44 S5]
  7. National Science Foundation [IGERT 0965983]

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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.

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