Jump to main content
Jump to site search

Issue 5-6, 2009
Previous Article Next Article

In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer

Author affiliations

Abstract

Activatable cell penetrating peptides (ACPPs) are novel in vivo targeting agents comprised of a polycationic cell penetrating peptide (CPP) connected via a cleavable linker to a neutralizing polyanion (Fig. 1A). Adsorption and uptake into cells are inhibited until the linker is proteolyzed. An ACPP cleavable by matrix metalloproteinase-2 (MMP-2) in vitro was the first one demonstrated to work in a tumor model in vivo, but only HT-1080 xenografts and resected human squamous cell carcinomas were tested. Generality to other cancer types, in vivo selectivity of ACPPs for MMPs, and spatial resolution require further characterization. We now show that ACPPs can target many xenograft tumor models from different cancer sites, as well as a thoroughly studied transgenic model of spontaneous breast cancer (mouse mammary tumor virus promoter driving polyoma middle T antigen, MMTV-PyMT). Pharmacological inhibitors and genetic knockouts indicate that current ACPPs are selective for MMP-2 and MMP-9 in the above in vivo models. In accord with the known local distribution of MMP activity, accumulation is strongest at the tumor–stromal interface in primary tumors and associated metastases, indicating better spatial resolution (<50 μm) than other currently available MMP-cleavable probes. We also find that background uptake of ACPPs into normal tissues such as cartilage can be decreased by appending inert macromolecules of 30–50 KDa to the polyanionic inhibitory domain. Our results validate an approach that should generally deliver imaging agents and chemotherapeutics to sites of invasion, tumor-promoting inflammation, and metastasis.

Graphical abstract: In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer

Back to tab navigation

Supplementary files

Publication details

The article was received on 10 Mar 2009, accepted on 29 Apr 2009 and first published on 11 May 2009


Article type: Paper
DOI: 10.1039/B904890A
Citation: Integr. Biol., 2009,1, 382-393
  •   Request permissions

    In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer

    E. S. Olson, T. A. Aguilera, T. Jiang, L. G. Ellies, Q. T. Nguyen, E. H. Wong, L. A. Gross and R. Y. Tsien, Integr. Biol., 2009, 1, 382
    DOI: 10.1039/B904890A

Search articles by author

Spotlight

Advertisements