One-pot synthesis of nanochain particles for targeting brain tumors

Abstract

To synthesize multi-component nanochains, we developed a simple ‘one-pot’ synthesis, which exhibited high yield and consistency. The nanochains particles consist of parent nanospheres chemically linked into a higher-order, chain-like assembly. The one-pot synthesis is based on the addition of two types of parent nanospheres in terms of their surface chemical functionality (e.g., decorated with PEG-NH2 or PEG-COOH). By reacting the two types of parent nanospheres at a specific ratio (~2:1) for a short period of time (~30 min) under rigorous stirring, nanochains were formed. For example, we show the synthesis of iron oxide nanochains with lengths of about 125 nm consisting of 3–5 constituting nanospheres. The chain-like shaped nanoparticle possessed a unique ability to target and rapidly deposit on the endothelium of glioma sites via vascular targeting. To target and image invasive brain tumors, we used iron oxide nanochains with the targeting ligand being the fibronectin-targeting peptide CREKA. Overexpression of fibronectin is strongly associated with the perivascular regions of glioblastoma multiforme and plays a critical role in migrating and invasive glioma cells. In mice with invasive glioma tumors, 3.7% of the injected CREKA-targeted nanochains was found in gliomas within 1 h. Notably, the intratumoral deposition of the nanochain was ~2.6-fold higher than its spherical variant. Using MR imaging, the precise targeting of nanochains to gliomas provided images with the exact topology of the disease including their margin of infiltrating edges and distant invasive sites.

Imaging breast cancer using a dual-ligand nanochain particle

“…The only difference was the higher clearance of the spherical IONP from the spleen compared to all the nanochain formulations. This was in good agreement with previous observations [5, 13, 38]. Further, the signal from the lungs and kidneys was negligible for all formulations.…”

“…The organ distribution of the dual-ligand nanochain was compared to a single-ligand nanochain, the non-targeted nanochain variant, and the parent IONP with a single ligand. In previous studies [13], the tissue deposition of targeted iron oxide nanoparticles was measured using ICP-OES, which provided direct measurement of iron concentration in tissues using ICP. However, the MR signal from tissues does not always correspond to the exact concentration of the iron oxide particles in tissues.…”

“…It should be noted that the spherical nanoparticles were the parent particles used for the fabrication of the nanochains. Our previous studies showed that deposition of targeted nanoparticles onto the endothelium of tumors is rapid and is maximized within 3 h after systemic administration [3, 5, 6, 13]. Thus, we selected the 3-hour time point as the terminal point when the tumors were perfused, excised, and homogenized.…”

Imaging breast cancer using a dual-ligand nanochain particle

“…We recently developed a new simple ‘one-pot’ synthetic concept for making iron oxide nanochains with high yield and consistency [ 13 ]. Fig 1a shows an illustration of the nanochain particles.…”

“…Further, the shape of the nanoparticle can dictate its targeting avidity [ 7 , 10 – 12 ]. Recently, we reported a new one-pot synthetic concept for making multicomponent chain-like nanoparticles (termed nanochains), which are comprised of about three iron oxide nanospheres chemically linked into a linear, chain-like assembly [ 13 ]. The chain-like shape of the nanoparticles facilitates geometrically enhanced multivalent attachment on vascular targets, resulting in rapid and effective deposition of the nanochains onto the endothelium of tumors [ 5 , 8 , 13 , 14 ].…”