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.

Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells

“…In addition, our absorption spectrum and aspect ratio results agree with the maximum absorption peak wavelengths and aspect ratios reported by Nikoobakht and Feng, who obtained, for example, 700 nm for GNRs of 2.7 aspect ratio, 728 nm for GNRs of 3.4 aspect ratio, and 760 nm for GNRs of 3.9 aspect ratio. 30,48 Pegylation mitigates gNr toxicity At present, CTAB-based GNRs [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] are well known to be toxic. To address this issue, a few modifications have been incorporated into published CTAB-GNR synthesis protocols.…”

“…Rod-shaped nanoparticles have the advantage of long axes that have large surface areas for enhanced interaction with the ECs on blood vessel walls ( Figure 1). 21 At present, the cetyltrimethylammonium bromide (CTAB)-based GNR synthesis protocols [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] produce GNRs with diameters that are too big for GCX-mediated permeability across the vessel wall. One common approach to GNR synthesis is the CTABmediated seed growth method used by Nikoobakht's and other research groups.…”

“…One common approach to GNR synthesis is the CTABmediated seed growth method used by Nikoobakht's and other research groups. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] This method utilizes CTAB solution and chloroauric acid (HAuCl 4 ). Combining these chemicals creates an Au(III)-CTAB complex, due to formation of an ion pair between the negatively charged AuCl 4 and the positive head groups of the CTAB micelles.…”

Target Site Delivery and Residence of Nanomedicines: Application of Quantitative Systems Pharmacology

“…Readers are referred to earlier reviews Li et al, 2012;Andar et al, 2014;Shang et al, 2014;Paliwal et al, 2015;Treuel et al, 2015;Au et al, 2016;Yang et al, 2016;Behzadi et al, 2017;Kinnear et al, 2017) for more details and the original citations. HER, human epidermal growth factor receptor; uPAR, urokinase-type plasminogen activator receptor.…”

Bottom-up self-assembly of heterotrimeric nanoparticles and their secondary Janus generations

“…[18][19][20] The impact of the size, shape, composition, aspect ratio and orientation of nanoparticles interacting with cells has been extensively reported. 3,[21][22][23] Nevertheless, there are few reports where the difference between Janus and spherical nanoparticles is directly compared.…”