Targeting of albumin-embedded paclitaxel nanoparticles to tumors.
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.
Karmali
Priya Prakash
PP
Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California 93106-9610, USA.
Kotamraju
Venkata Ramana
VR
Kastantin
Mark
M
Black
Matthew
M
Missirlis
Dimitris
D
Tirrell
Matthew
M
Ruoslahti
Erkki
E
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
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D004337:Drug Carriers; D010455:Peptides; D017239:Paclitaxel