HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting.
Targeted delivery of intracellularly active diagnostics and therapeutics in vivo is a major challenge in cancer nanomedicine. A nanocarrier should possess long circulation time yet be small and stable enough to freely navigate through interstitial space to deliver its cargo to targeted cells. Herein, it is shown that by adding targeting ligands to nanoparticles that mimic high-density lipoprotein (HDL), tumor-targeted sub-30-nm peptide-lipid nanocarriers are created with controllable size, cargo loading, and shielding properties. The size of the nanocarrier is tunable between 10 and 30 nm, which correlates with a payload of 15-100 molecules of fluorescent dye. Ligand-directed nanocarriers targeting epidermal growth factor receptor (EGFR) are confirmed both in vitro and in vivo. The nanocarriers show favorable circulation time, tumor accumulation, and biodistribution with or without the targeting ligand. The EGFR targeting ligand is proved to be essential for the EGFR-mediated tumor cell uptake of the nanocarriers, a prerequisite of intracellular delivery. The results demonstrate that targeted HDL-mimetic nanocarriers are useful delivery vehicles that could open new avenues for the development of clinically viable targeted nanomedicine.
Zhang
Zhihong
Z
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, ON M5G 1L7, Canada.
Chen
Juan
J
Ding
Lili
L
Jin
Honglin
H
Lovell
Jonathan F
JF
Corbin
Ian R
IR
Cao
Weiguo
W
Lo
Pui-Chi
PC
Yang
Mi
M
Tsao
Ming-Sound
MS
Luo
Qingming
Q
Zheng
Gang
G
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D018716:Molecular Mimicry; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D015203:Reproducibility of Results; D023041:Xenograft Model Antitumor Assays
D004337:Drug Carriers; D008075:Lipoproteins, HDL; D010455:Peptides; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors