Vascular changes in tumors resistant to a vascular disrupting nanoparticle treatment.

TitleVascular changes in tumors resistant to a vascular disrupting nanoparticle treatment.
Publication TypeJournal Article
Year of Publication2017
AuthorsSharma S, Mann AP, Mölder T, Kotamraju VRamana, Mattrey R, Teesalu T, Ruoslahti E
JournalJ Control Release
Date Published2017 Oct 13

Anti-angiogenic and vascular disrupting therapies rely on the dependence of tumors on new blood vessels to sustain tumor growth. We previously reported a potent vascular disrupting agent, a theranostic nanosystem consisting of a tumor vasculature-homing peptide (CGKRK) fused to a pro-apoptotic peptide [D(KLAKLAK)2] coated on iron oxide nanoparticles. This nanosystem showed promising therapeutic efficacy in glioblastoma (GBM) and breast cancer models. However, complete control of the tumors was not achieved, and some tumors became non-responsive to the treatment. Here we examined the non-responder phenomenon in an aggressive MCF10-CA1a breast tumor model. In the treatment-resistant tumors we noted the emergence of CD31-negative patent neovessels and a concomitant loss of tumor homing of the nanosystem. In vivo phage library screening in mice bearing non-responder tumors showed that compared to untreated and treatment-sensitive tumors, treatment sensitive tumors yield a distinct landscape of vascular homing peptides characterized by over-representation of peptides that target αv integrins. Our approach may be generally applicable to the development of targeted therapies for tumors that have failed treatment.

Alternate JournalJ Control Release
PubMed ID29030222