Enzyme-responsive multistage vector for drug delivery to tumor tissue

Yu Mi, Joy Wolfram, Chaofeng Mu, Xuewu Liu, Elvin Blanco, Haifa Shen, Mauro Ferrari

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Various nanodelivery systems have been designed to release therapeutic agents upon contact with specific enzymes. However, enzyme-triggered release typically takes place in the tissue interstitium, thereby resulting in the extracellular delivery of drugs. Here, we have designed an enzyme-stimulated multistage vector (ESMSV), which enables stimulus-triggered release of drug-encapsulated nanoparticles from a microparticle. Specifically, polymeric nanoparticles with a surface matrix metalloproteinase-2 (MMP2) peptide substrate were conjugated to the surface of porous silicon microparticles. In the presence of MMP2, the polymeric nanoparticles were released into the tumor interstitium. This platform can be used to attain triggered drug release, while simultaneously facilitating the cellular internalization of drugs. The results indicate that nanoparticle release was MMP2-specific and resulted in improved intracellular uptake of hydrophobic agents in the presence of MMP2. Furthermore, in a mouse model of melanoma lung metastasis, systemic delivery of ESMSVs caused a substantial increase in intracellular accumulation of agents in cancer cells in comparison to delivery with non-stimulus-responsive particles.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalPharmacological Research
Volume113
DOIs
StatePublished - Nov 1 2016

Keywords

  • Enzyme-responsive release
  • Lung metastasis
  • MMP2
  • Multistage vector
  • Porous silicon

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Enzyme-responsive multistage vector for drug delivery to tumor tissue'. Together they form a unique fingerprint.

Cite this