期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 13, 期 6, 页码 1869-1878出版社
ELSEVIER
DOI: 10.1016/j.nano.2017.04.009
关键词
ApoA-I mimetic peptide; HDL; SR-bi; Tumor targeting; Surface modification
资金
- AHA grants [13SDG17230049, 15PRE25090050, 16POST27760002]
- NIH [K22AI097291-01, R01EB022563, R01CA210273, R01GM113832, R21NS091555]
- MTRAC for Life Sciences
- University of Michigan Comprehensive Cancer Center Forbes Institute for Cancer Discovery
- Upjohn award
- MCubed grant
- Melanoma Research Alliance [348774]
- NSF CAREER Award [1553831]
Synthetic high-density lipoprotein nanoparticles (sHDL) are a valuable class of nanomedicines with established animal safety profile, clinical tolerability and therapeutic efficacy for cardiovascular applications. In this study we examined how the scavenger receptor B-Imediated (SR-BI) tumor-targeting ability of sHDL, long plasma circulation half-life, and small particle size (9.6 +/- 0.2 nm) impacted sHDL accumulation in SR-BI positive colorectal carcinoma cells, 3D tumor spheroids, and in vivo xenografts. We compared tumor accumulation of sHDL with that of liposomes (LIP, 130.7 +/- 0.8 nm), pegylated liposomes (PEG-LIP, 101 +/- 2 nm), and pegylated sHDL (12.1 +/- 0.1 nm), all prepared with the same lipid components. sHDL penetrated deep (210 mu m) into tumor spheroids and exhibited 12-and 3-fold higher in vivo solid tumor accumulation, compared with LIP (p < 0.01) and PEG-LIP (p < 0.05), respectively. These results suggest that sHDL with established human safety possess promising intrinsic tumor-targeted properties. (C) 2017 Elsevier Inc. All rights reserved.
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