title: Mechanism for the Cellular Uptake of Targeted Gold Nanorods of Defined Aspect Ratios.
abstract: Biomedical applications of non-spherical nanoparticles such as photothermal therapy and molecular imaging require their efficient intracellular delivery, yet reported details on their interactions with the cell remain inconsistent. Here, the effects of nanoparticle geometry and receptor targeting on the cellular uptake and intracellular trafficking are systematically explored by using C166 (mouse endothelial) cells and gold nanoparticles of four different aspect ratios (ARs) from 1 to 7. When coated with poly(ethylene glycol) strands, the cellular uptake of untargeted nanoparticles monotonically decreases with AR. Next, gold nanoparticles are functionalized with DNA oligonucleotides to target Class A scavenger receptors expressed by C166 cells. Intriguingly, cellular uptake is maximized at a particular AR: shorter nanorods (AR = 2) enter C166 cells more than nanospheres (AR = 1) and longer nanorods (AR = 4 or 7). Strikingly, long targeted nanorods align to the cell membrane in a near-parallel manner followed by rotating by ≈90° to enter the cell via a caveolae-mediated pathway. Upon cellular entry, targeted nanorods of all ARs predominantly traffic to the late endosome without progressing to the lysosome. The studies yield important materials design rules for drug delivery carriers based on targeted, anisotropic nanoparticles.
authors.affiliation: Department of Electronic Engineering (Biomedical Engineering), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Electronic Engineering (Biomedical Engineering), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.|Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Electronic Engineering (Biomedical Engineering), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.|Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong, China.
authors.forename: Wing-Yin
authors.initials: WY
authors.lastname: Yung
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong, China.
authors.forename: Ken Cham-Fai
authors.initials: KC
authors.lastname: Leung
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Ho Yin Edwin
authors.initials: HY
authors.lastname: Chan
authors.affiliation: Department of Electronic Engineering (Biomedical Engineering), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. jchchoi@ee.cuhk.edu.hk.|Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. jchchoi@ee.cuhk.edu.hk.
authors.forename: Chung Hang Jonathan
authors.initials: CH
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D006046:Gold / Q000737:chemistry*; D051379:Mice; D008954:Models, Biological; D043942:Nanotubes / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D011092:Polyethylene Glycols; D006046:Gold; D004247:DNA
keywords: anisotropic nanoparticles; aspect ratio; cellular uptake; intracellular trafficking; receptor targeting