Quantitative synchrotron X-ray fluorescence study of the penetration of transferrin-conjugated gold nanoparticles inside model tumour tissues

Abstract

The next generation of therapeutic nanoparticles in the treatment of cancer incorporate specific targeting. There is implicit importance in understanding penetration of targeted nanomedicines within tumour tissues via accurate and quantitative temporospatial measurements. In this study we demonstrate the potential of state-of-the-art synchrotron X-ray fluorescence microscopy (XFM) to provide such insights. To this end, quantitative mapping of the distribution of transferrin-conjugated gold nanoparticles inside multicellular tumour spheroids was achieved using XFM and compared with qualitative data obtained using reflectance confocal microscopy. Gold nanoparticles conjugated with human transferrin with a narrow size-distribution and high binding affinity to tumour cells were prepared as confirmed by cellular uptake studies performed on 2D monolayers. Although the prepared 100 nm transferrin-conjugated gold nanoparticles had high targeting capability to cancer cells, penetration inside multicellular spheroids was limited even after 48 hours as shown by the quantitative XFM measurements. The rapid, quantitative and label-free nature of state-of-the-art synchrotron XFM make it an ideal technology to provide the structure-activity relationship understanding urgently required for developing the next generation of immuno-targeted nanomedicines.

Development of docetaxel nanocrystals surface modified with transferrin for tumor targeting

“…Transferrin is widely used for the surface modification of NPs and for tumor targeting 46,47. The cells express transferrin receptors that interact with transferrin of the delivery system.…”

Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78

“…Recently, researchers have found that some specific molecules used as targeting agents, such as carbohydrate, 10 folic acid, 11,12 transferrin, 13,14 and some peptides, 15,16 could be modified onto the surface of NPs and achieve active targeting therapy with high specificity, selectivity, and affinity through coupling targeting molecules with their specific receptor expressed on the cell surface.…”

An image processing application for quantitative cross-correlative microscopy for large cell-populations: a gold nanoparticle radiosensitisation study

“…A AuNP solution (0.6 nM) was prepared by the standard sodium citrate reduction method proposed by Enüstün and Turkevich (1963) and widely published in the literature (Liu et al, 2014(Liu et al, , 2015Cruje and Chithrani, 2015). AuNPs were first treated with a polyethylene glycol (PEG) solution consisting of a mix of short-chain (458.6 Da) to long-chain (2000 Da) PEG (Rapp Polymere, Tübingen, Germany) at a volume ratio of 4:1 based on a previously established protocol (Liu and Thierry, 2012).…”

“…Inorganic NP content can be obtained in bulk assays with the most commonly used technique being inductively coupled plasma mass spectrometry (ICP-MS) (Subiel et al ., 2016). Laser ablation ICP-MS (Drescher et al ., 2012) and reflectance confocal microscopy are methods that have been applied to quantifying inorganic NP content at the single-cell level; however, these methods typically only provides qualitative measures of NP content (Liu et al ., 2014). Recent advances in synchrotron X-ray fluorescence (XRF) detector technology have now made it possible for statistically significant numbers of cells to be analysed for elemental content in within manageable time frames (Vogt and Lanzirotti, 2013; Kempson et al ., 2014).…”