Tumor suppression via paclitaxel-loaded drug carriers that target inflammation marker upregulated in tumor vasculature and macrophages.

TitleTumor suppression via paclitaxel-loaded drug carriers that target inflammation marker upregulated in tumor vasculature and macrophages.
Publication TypeJournal Article
Year of Publication2013
AuthorsPark S, Kang S, Chen X, Kim EJ, Kim J, Kim N, Kim J, Jin MM
JournalBiomaterials
Volume34
Issue2
Pagination598-605
Date Published2013 Jan
ISSN1878-5905
KeywordsAnimals, Antineoplastic Agents, Phytogenic, Cell Line, Tumor, Drug Carriers, Drug Delivery Systems, Female, Humans, Inflammation, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, Macrophages, Mice, Mice, SCID, Nanoparticles, Neoplasms, Paclitaxel, Protein Structure, Tertiary, Recombinant Proteins
Abstract

Clinically approved chemotherapeutic nanoparticles may provide advantages over free drugs by achieving slower clearance and preferential accumulation in tumors. However, the lack of leaky vasculatures can create barriers to the permeation of ~100 nm-sized nanoparticles in solid tumors. We hypothesized that nanoparticles designed to target both tumor and tumor stroma would penetrate deeper into the tumors. To construct such comprehensive drug carriers, we utilized cross-linked amphiphilic polymer nanoparticles and functionalized them to target ICAM-1, a biomarker prevalent in various tumors and inflamed tumor stroma. The targeting moiety was derived from the modular domain present in α(L) integrin, which was engineered for high affinity and cross-reactivity with human and murine ICAM-1. ICAM-1-selective delivery of paclitaxel produced potent tumor suppression of not only ICAM-1-positive cervical cancer cells but also ICAM-1-negative tumors, presumably by causing cytotoxicity in tumor-associated endothelium (CD31(+)) and macrophages (CD68(+)) over-expressing ICAM-1. Contrary to the strategies of targeting only the tumor or specific tumor stromal constituents, we present a strategy in delivering therapeutics to the major cellular components of solid tumors. Drug carriers against inflammation-biomarkers may be effective against many different types of tumors, while being less susceptible to the highly mutable nature of tumor markers.

DOI10.1016/j.biomaterials.2012.10.004
Alternate JournalBiomaterials
PubMed ID23099063
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065