Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications

Abstract

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T 2 relaxivity of ∼223 mM −1 s −1 and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.

Penicillamine-Capped Red-Emitting Gold Nanoclusters for Therapeutic Application

“…The kidney poses a critical physiological barrier to filtering blood components based on size cut-off. The factors, such as the size of d -penicillamine-stabilized Au NCs being less than 6 nm and a steady near-neutral zeta potential, favor them toward renal clearance. , ICP–MS analysis of various organs 24 h post-injection showed a high gold accumulation (∼34% ID/g) in the kidneys compared to that in the liver and spleen (Figure B). This result correlates with reported urinary clearance of DPA and similarly sized metal NCs after possible evasion of any protein fouling and aggregation during peripheral circulation.…”

Preclinical safety assessment of photoluminescent metal quantum clusters stabilized with autologous serum proteins for host specific theranostics

“…However on Day 28, all the organs including liver possessed only marginal quantity (0.08% ID/g for liver and spleen) of MQCNS. While prior reports show that kidney is the most preferred route of excretion for nanoparticles with size less than 6-8nm [41][42][43], albumin stabilized AuQCs is an exception due to its retention from passing through healthy glomerular basal membrane [44]. While there is no single pathway of albumin degradation, most studies have reported that GI tract is a significant site of albumin catabolism (~ 40-70%) in normal individuals [45].…”

Renal clearable magnetic nanoparticles for magnetic resonance imaging and guided therapy

“…These results confirmed the biodegradability of HPIO@ZDS and its rapid clearance by the kidney. Similarly, Pranjali et al designed and synthesized iron oxide and gold NPs assembled into decomposable nanoclusters, which decompose under physiological conditions and are cleared through both hepatobiliary and renal pathways (Yadav et al, 2022). These biodegradable NPs provide an exciting opportunity for the design of kidney‐clearable NPs.…”