Multistage nanoparticle delivery system for deep penetration into tumor tissue

Current Food and Drug Administration-approved cancer nanotherapeutics, which passively accumulate around leaky regions of the tumor vasculature because of an enhanced permeation and retention (EPR) effect, have provided only modest survival benefits. This suboptimal outcome is likely due to physiological barriers that hinder delivery of the nanotherapeutics throughout the tumor. Many of these nanotherapeutics are ≈ 100 nm in diameter and exhibit enhanced accumulation around the leaky regions of the tumor vasculature, but their large size hinders penetration into the dense collagen matrix. Therefore, we propose a multistage system in which 100-nm nanoparticles "shrink" to 10-nm nanoparticles after they…

• UD
  U.S. Department of Defense

  Awards: W81XWH-10-1-0016, W81XWH
• SG
  Susan G. Komen for the Cure
• NI
  National Institutes of Health

  Awards: CA096915, R01-CA126642, CA126642, CA080124, R01-CA115767, W81XWH, P01-CA080124, 9729592, CA085140, CA115767, CA119349
• NC
  National Cancer Institute

  Awards: CA096915, W81XWH-10-1-0016, P01-CA080124, R01-CA126642, 1U54-CA119349, R01-CA085140, R01-CA096915, R01-CA115767
• DO
  Division of Chemistry