Controlled Assembly of Biodegradable Plasmonic Nanoclusters for Near-Infrared Imaging and Therapeutic Applications

Abstract

Metal nanoparticles with surface plasmon resonance (SPR) in the near-infrared region (NIR) are of great interest for imaging and therapy. Presently, gold nanoparticles with NIR absorbance are typically larger than 50nm, above the threshold size of ~5 nm required for efficient renal clearance. As these nanoparticles are not biodegradable, concerns about long-term toxicity have restricted their translation into the clinic. Here, we address this problem by developing a flexible platform for the kinetically-controlled assembly of sub-5 nm ligand-coated gold particles to produce metal/polymer biodegradable nanoclusters smaller than 100 nm with strong NIR absorbance for multimodal application. A key novel feature of the proposed synthesis is the use of weakly adsorbing biodegradable polymers that allows tight control of nanocluster size and, in addition, results in nanoclusters with unprecedented metal loadings, and thus optical functionality. Over time, the biodegradable polymer stabilizer degrades under physiological conditions that leads to disassembly of the nanoclusters into sub-5nm primary gold particles which are favorable for efficient body clearance. This synthesis of polymer/inorganic nanoclusters combines the imaging contrast and therapeutic capabilities afforded by the NIR-active nanoparticle assembly with the biodegradability of a polymer stabilizer.

Evaluation of gold nanotracers to track adipose-derived stem cells in a PEGylated fibrin gel for dermal tissue engineering applications

“…It is known that both somatic and stem cells take up nanoparticles via early endosomes, are stored in late endosomes and lysosomes, and are eventually excreted from the cell. 31 In the current study, strong PA signals were detected from the ASC-cultured gels for more than 2 weeks. Even though the GNTs in ASC/gels (at 750 nm) showed significantly brighter PA signals on day 16, it was shown here that the degradation of PFGs, which occurred in the second week of the culture period, correlated with the increased PA signals due to the increased concentration of GNTs/volume of gel.…”

“…This is due to the aggregation-induced plasmon resonance coupling, a phenomenon which is well described in the literature. [31][32] In addition, GNTs in the cells showed higher UV-visible absorbance than cells without GNT treatment. The effects of GNTs on cellular behavior and function can be varied depending on the cell type and particle features such as size, shape, and surface characteristics.…”

“…The effects of GNTs on cellular behavior and function can be varied depending on the cell type and particle features such as size, shape, and surface characteristics. 31 Adverse effects such as organelle disruption, membrane breakdown, and apoptosis can be induced. 30 However, the current study demonstrated no significant differences between ASCs loaded with GNTs compared to those without GNTs in respect to cell morphology, viability, or proliferation.…”

Cytotoxicity of gold nanoclusters in human liver cancer cells

“…Inorganic nanoparticles are difficult to biodegrade and induce long-term toxicity, which hinders their application in clinical practice. 9 Particles smaller than 5.5 nm can be rapidly and efficiently removed by the kidneys, 9,10 which allows them to be used safely in the clinic. Recently, Zhang et al 10 reported that the renal clearance rate of glutathione-protected Au NCs (2.1 nm) was maximum at 2 hours after injection, and only 6% of Au could be detected in mice at 28 days.…”

Synthesis of Iron Oxide Nanoclusters with Enhanced Magnetization and Their Applications in Pulsed Magneto-Motive Ultrasound Imaging

“…In this method, the polymers play a role in holding the colloidal particles together to form spherical aggregates. 38 In other studies, synthesis of kinetically controlled, near-IR active, gold-coated IO nanoclusters from a dispersion of IO NPs, were reported. 8,9 Overall, magnetic nanoclusters consisting of primary magnetic NPs assembled through various noncovalent interactions provide high magnetization and good colloidal stability.…”