In situ polymerization on nanoscale metal-organic frameworks for enhanced physiological stability and stimulus-responsive intracellular drug delivery

Biomaterials. 2019 Oct:218:119365. doi: 10.1016/j.biomaterials.2019.119365. Epub 2019 Jul 15.

Abstract

Metal-organic framework (MOF) nanoparticles have shown great potential as carrier platforms in theranostic applications. However, their poor physiological stability in phosphate-based media has limited their biological applications. Here, we studied the dissociation of MOF nanoparticles under physiological conditions, both in vitro and in vivo, and developed an in situ polymerization strategy on MOF nanoparticles for enhanced stability under physiological conditions and stimulus-responsive intracellular drug release. With polymer wrapped on the surface serving as a shield, the nanoscale MOFs were protected from decomposition by phosphate ions or acid and prevented the loaded cargos from leaking. An in vivo positron emission tomography (PET) study of 64Cu-labelled porphyrinic MOF indicated prolonged circulation time of the in situ polymerized MOF nanoparticles and greater tumor accumulation than unmodified MOF nanoparticles. With enhanced stability, cargos loaded into MOF nanoparticles or prodrugs conjugated on the surface can be efficiently delivered and released upon stimulus-responsive cleavage.

Keywords: Metal-organic frameworks; PET; Polymerization; Stimulus-responsive drug delivery.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Drug Delivery Systems / methods*
  • Metal-Organic Frameworks*
  • Nanoparticles / chemistry
  • Polymerization
  • Positron-Emission Tomography

Substances

  • Metal-Organic Frameworks