Image-guided local delivery strategies enhance therapeutic nanoparticle uptake in solid tumors

ACS Nano. 2013 Sep 24;7(9):7724-33. doi: 10.1021/nn4023119. Epub 2013 Aug 20.

Abstract

Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome many of the limitations of current cancer chemotherapeutics. However, a major challenge to many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical adoption of NP therapeutics. To overcome these limitations, we have adapted the techniques of image-guided local drug delivery to develop nanoablation and nanoembolization. Nanoablation is a tumor ablative strategy that employs image-guided placement of electrodes into tumor tissue to electroporate tumor cells, resulting in a rapid influx of NPs that is not dependent on cellular uptake machinery or stage of the cell cycle. Nanoembolization involves the image-guided delivery of NPs and embolic agents directly into the blood supply of tumors. We describe the design and testing of our innovative local delivery strategies using doxorubicin-functionalized superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We demonstrate that local delivery techniques result in significantly increased intratumoral DOX-SPIO uptake, with limited off-target delivery in tumor-bearing animal models. The techniques described are versatile enough to be extended to any NP platform, targeting any solid organ malignancy that can be accessed via imaging guidance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics*
  • Embolization, Therapeutic / methods*
  • Magnetic Resonance Imaging, Interventional / methods*
  • Magnetite Nanoparticles* / administration & dosage
  • Male
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Magnetite Nanoparticles
  • Doxorubicin