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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 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).

Graphitic carbon nitride (also known as g-CN or g-C₃N₄) has the intrinsic ability to generate electron–hole pairs under visible light illumination, resulting in the generation of reactive oxygen species (ROS). We report g-CN quantum dots (g-CNQDs) as a standalone photodynamic transducer for imparting significant oxidative stress in glioma cells, manifested by the loss of mitochondrial membrane potential. With an optimized treatment time, visible light source, and exposure window, the photodynamic treatment with g-CNQDs could achieve ∼90% cancer cell death via apoptosis. The g-CNQDs, otherwise biocompatible with normal cells up to 5 mg/mL, showed ∼20% necrotic cancer cell death in the absence of light due to membrane damage induced by a charge shielding effect at the acidic pH prevailing in the tumor environment. Acute toxicity analysis in C57BL/6 mice with intravenously injected g-CNQDs at a 20 mg/kg dose showed no signs of inflammatory response or organ damage.

More info: Pranjali Yadav, Mimansa, Kamalakannan Kailasam*, Asifkhan Shanavas*, ACS Applied Bio Materials, 2022(https://doi.org/10.1021/acsabm.1c01219)

Pranjali et al prepared a mesoporous magnetic nanohybrid functionalized with 14 wt% carbon nitride (CN) and loaded with curcumin (Cur) for combination platform for photodynamic therapy and magnetic hyperthermia. CN-Cur complexes on the nanoparticle surface facilitate fast charge separation of hole-electrons under blue LED light irradiation and subsequent singlet oxygen generation. Cur release from the nanoparticle was significant only when exposed to both lysosomal pH (pH=5.2) and an alternating current magnetic field (AMF). The mesoporous magnetic carbon nitride (MMCN) caused a 350% increase in the level of intracellular ROS as compared to the light-exposed untreated control group. The nanohybrid was non-hemolytic and found to be biocompatible with HUVEC cells at concentrations up to 360 µg/mL. A similar concentration under AMF exposure caused a localized temperature rise of 4.2 °C and resulted in a60% reduction in C6 cell viability. The cancer cell death further increased up to 80% under sequential exposure to light and AMF. The combinatorial treatment exerted significant cytoskeletal and nuclear damage in the cancer cells as assessed by confocal microscopy. The nanohybrid also exhibited relaxivity of 88 mM^-1 s^-1, imparting significant T₂weighted contrast to the cancer cells.

More info: Pranjali Yadav, Cheng Zhang, Andrew K. Whittaker, Kamalakannan Kailasam and Asifkhan Shanavas, Magnetic and Photocatalytic Curcumin Bound Carbon Nitride Nanohybrids for Enhanced Glioma Cell Death, ACS Biomater. Sci. Eng. 2019 (https://doi.org/10.1021/acsbiomaterials.9b01224)