PEG-like Multimodal Nanoprobes for Imaging Enhanced Permeability Retention

点击翻译按钮获取中文摘要

Abstract PEG-like Multimodal Nanoprobes (PMN's) are passively targeted nanomaterials for determining the mechanism of retention obtained with enhanced permeability and retention (EPR), for imaging and modeling EPR pre-clinically, and for the eventual imaging of the EPR biomarker in the clinic. EPR is the slow accumulation (12-72 h post injection) of long-circulating nanomedicines (e.g. drug-polymer conjugates, liposomes) in tumors and inflammatory lesions. PMN's consist of DOTA, a PEG, and a fluorochrome attached to a (DOTA)Lys-Cys scaffold. PEG improves fluorochrome performance and endows a PMN with a PEG- determined (rather than fluorochrome-determined) behavior in biological systems. PMN's differ from other EPR nanoprobes (liposomes, albumin, dextrans) by exhibiting a surprising renal (rather than hepatic) elimination, even when the PEG determined dimensions of a PMN exceed the size limit of glomerular filtration, and even when the PMN exhibits the extremely slow whole body clearance needed for a large EPR uptake. The PMN's fluorochrome allows fluorescence-based determination of PMN in tissues (post injection microscopy) or cultured cells (FACS), and will be used to determine the mechanism of PMN retention. DOTA allows 111In3+ radiolabeling for modeling EPR by SPECT and for eventual clinical imaging by SPECT or PET. PMN-EPR imaging maybe employed for the primary detection of tumors or inflammatory lesions, or to stratify patients for the use of long circulating nanomedicines (e.g. liposomes) used in the treatment of their cancer or arthritis.