Probing Interactions between AuNPs/AgNPs and Giant Unilamellar Vesicles (GUVs) Using Hyperspectral Dark-field Microscopy

Abstract

Noble metallic nanoparticles (NPs) such as gold and silver nanoparticles (AuNPs and AgNPs) have been shown to exhibit anti-tumor effect in anti-angiogenesis, photothermal and radio therapeutics. On the other hand, cell membranes are critical locales for specific targeting of cancerous cells. Therefore, NP-membrane interactions need be studied at molecular level to help better understand the underlying physicochemical mechanisms for future applications in cancer nanotechnology. Herein, we report our study on the interactions between citrate stabilized colloidal AuNPs/AgNPs (10 nm in size) and giant unilamellar vesicles (GUVs) using hyperspectral dark-field microscopy. GUVs are large model vesicle systems well established for the study of membrane dynamics. GUVs used in this study were prepared with dimyristoyl phosphatidylcholine (DMPC) and doped with cholesterol at various molar concentrations. Both imaging and spectral results support that AuNPs and AgNPs interact very differently with GUVs, i.e., AuNPs tend to integrate in between the lipid bilayer and form a uniform golden-brown crust on vesicles, whereas AgNPs are bejeweled on the vesicle surface as isolated particles or clusters with much varied configurations. The more disruptive capability of AuNPs is hypothesized to be responsible for the formation of golden brown crusts in AuNP-GUV interaction. GUVs of 20 mol% CHOL:DMPC were found to be a most economical concentration for GUVs to achieve the best integrity and the least permeability, consistent with the finding from other phase studies of lipid mixture that the liquid-ordered domains have the largest area fraction of the entire membrane at around 20 mol% of cholesterol.

Size dependency of gold nanoparticles interacting with model membranes

“…One of the key events contributing to nanotoxicity is the interaction of ENMs with phospholipid membranes. For this reason, lipid membranes such as phospholipid vesicles are commonly exploited as a minimal model system for investigating the biological impact of ENMs [3][4][5][6][7] . It has been demonstrated that nanoparticles can be internalised within both cells or model membranes via non-specific interactions, in the absence of receptor-mediated uptake 4,6,8 .…”

“…Among the many possible ENMs, spherical gold nanoparticles (AuNPs) have emerged as promising candidates for biomedical diagnostic, therapeutic and photoelectrochemical applications [14][15][16] due to their facile surface chemistry, ease of synthesis and tuneable size. Depending on the specific AuNPs, membrane and dispersant properties, various interaction outcomes have been observed 5,6,12,[17][18][19] . For example, cationic 20 or hydrophobically 12 functionalised AuNPs (<5 nm) can successfully be internalised within the membrane bilayer.…”

“…1a). We employ citrate-stabilised AuNPs with a diameter ranging from 5 to 60 nm (i.e., 5,10,25,35,50 and 60 nm) and two formulations of unilamellar liposome (diameter of 180 nm): POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) and DOPC (1,2-dileoyl-sn-glycero-3-phosphocholine). Both POPC and DOPC (lipid structure in Fig.…”

Dark-Field Microscopy: Recent Advances in Accurate Analysis and Emerging Applications

“…By using hyperspectral DFM, Lu et al probed the interactions of giant unilamellar vesicles (GUVs) between noble metal nanoparticles, such as gold and silver nanoparticles. These two kinds of nanoparticles displayed very different states on the GUVs, including the distribution position and the clustering states . Xiao et al investigated the diffusion behavior of viral capsid protein (VCP)-coated gold nanoparticles on living cell membranes.…”

<p>Review of the Application of Nanovesicles and the Human Interstitial Fluid in Gastrointestinal Premalignant Lesion Detection, Diagnosis, Prognosis and Therapy</p>

“…Thus, they can be used as biomarkers in the early diagnosis of GI tumors 9. Synthetic NVs can be sub-divided into two groups: a conjugate mixture of nanoparticles (NPs) and vesicles such as the quantum dots (QDs) which are widely used in biomedical sensing and imaging applications;10 and human-engineered exosomes with diameters ranging from 50 to 200nm 11. The tumor-derived exosomes (TEXs), which carry proteins and RNAs (including microRNAs and messenger RNAs), are malignant vesicles that are prevalent in the serum of cancer patients.…”