Degradable theranostic nanoparticle

Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications

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 T2 relaxivity of 223 mM–1 s–1and 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.

More info: Pranjali Yadav, Mimansa, Rafika Munawara, Kanchan Kapoor, Shubhra Chaturvedi, Kamalakannan Kailasam, Samir Kumar Biswas, Dhirendra Bahadur, Rohit Srivastava, Anil Kumar Mishra, Asifkhan Shanavas*, ACS Biomaterials Science & Engineering, 2022 (https://doi.org/10.1021/acsbiomaterials.1c01579).

Degradable theranostic nanoparticle