Light induced drug delivery into cancer cells

Yosi Shamay, Lily Adar, Gonen Ashkenasy, Ayelet David

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin (52RRMKWKK58) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, d(KLAKLAK)2, into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.

Original languageEnglish
Pages (from-to)1377-1386
Number of pages10
JournalBiomaterials
Volume32
Issue number5
DOIs
StatePublished - 1 Feb 2011

Keywords

  • Caged peptides
  • Cell-penetrating peptides
  • Drug delivery
  • HPMA copolymers
  • Light activation

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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