title: Targeting of albumin-embedded paclitaxel nanoparticles to tumors.
abstract: We have used tumor-homing peptides to target abraxane, a clinically approved paclitaxel-albumin nanoparticle, to tumors in mice. The targeting was accomplished with two peptides, CREKA and LyP-1 (CGNKRTRGC). Fluorescein (FAM)-labeled CREKA-abraxane, when injected intravenously into mice bearing MDA-MB-435 human cancer xenografts, accumulated in tumor blood vessels, forming aggregates that contained red blood cells and fibrin. FAM-LyP-1-abraxane co-localized with extravascular islands expressing its receptor, p32. Self-assembled mixed micelles carrying the homing peptide and the label on different subunits accumulated in the same areas of tumors as LyP-1-abraxane, showing that Lyp-1 can deliver intact nanoparticles into extravascular sites. Untargeted, FAM-abraxane was detected in the form of a faint meshwork in tumor interstitium. LyP-1-abraxane produced a statistically highly significant inhibition of tumor growth compared with untargeted abraxane. These results show that nanoparticles can be effectively targeted into extravascular tumor tissue and that targeting can enhance the activity of a therapeutic nanoparticle.
authors.affiliation: Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California 93106-9610, USA.
authors.forename: Priya Prakash
authors.initials: PP
authors.lastname: Karmali
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.forename: Mark
authors.initials: M
authors.lastname: Kastantin
authors.forename: Matthew
authors.initials: M
authors.lastname: Black
authors.forename: Dimitris
authors.initials: D
authors.lastname: Missirlis
authors.forename: Matthew
authors.initials: M
authors.lastname: Tirrell
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D004337:Drug Carriers; D010455:Peptides; D017239:Paclitaxel