Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix

Alessandro Parodi, Seth G. Haddix, Nima Taghipour, Shilpa Scaria, Francesca Taraballi, Armando Cevenini, Iman K. Yazdi, Claudia Corbo, Roberto Palomba, Sm Z. Khaled, Jonathan O. Martinez, Brandon S. Brown, Lucas Isenhart, Ennio Tasciotti

Research output: Contribution to journalArticle

Abstract

Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br-MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.

Original languageEnglish
Pages (from-to)9874-9883
Number of pages10
JournalACS Nano
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 28 2014

Keywords

  • Bromelain
  • cancer
  • cellular uptake
  • extracellular matrix digestion
  • mesoporous silica nanoparticle modification

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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