Selective Organ-Targeting Hafnium Oxide Nanoparticles with Multienzyme-Mimetic Activities Attenuate Radiation-Induced Tissue Damage.

Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, radiosensitivity indices are evaluated of diverse normal organs as a genomic predictor of radiation susceptibility. Selective ORgan-Targeting (SORT) hafnium oxide nanoparticles (HfO2 NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO2 NPs like Hensify are commonly radioenhancers, but SORT HfO2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. A universal methodology is proposed to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition.

Correction: LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research.

Correction for 'LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research' by Dhiraj Kumar et al., J. Mater. Chem. B, 2023, 11, 1916-1928, https://doi.org/10.1039/D2TB02416K.

LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research.

Emerging multifunctional nanoparticulate formulations take advantage of nano-meter scale size and surface chemistry to work as a therapeutic delivery agent and a diagnostic tool for non-invasive real-time monitoring using imaging technologies. Here, we evaluate the selective uptake of 18 nm and 80 nm sized gold nanoparticles (AuNPs) by SKOV3 (4 times higher) ovarian cancer (OC) cells (compared to OVCAR5) in vitro, quantified by inductively coupled plasma (ICP) and MARS spectral photon-counting CT imaging (MARS SPCCT). Based on in vitro analysis, pristine AuNPs (18 nm) and surface modified AuNPs (18 nm) were chosen as a contrast agent for MARS SPCCT. The chemical analysis by FTIR spectroscopy confirmed the luteinizing hormone-releasing hormone (LHRH) conjugation to the AuNPs surface. For the first time, LHRH conjugated AuNPs were used for in vitro and selective in vivo OC targeting. The ICP-MS analysis confirmed preferential uptake of LHRH modified AuNPs by organs residing in the abdominal cavity with OC nodules (pancreas: 0.46 ng mg-1, mesentery: 0.89 ng mg-1, ovary: 1.43 ng mg-1, and abdominal wall: 2.12 ng mg-1) whereas the MARS SPCCT analysis suggested scattered accumulation of metal around the abdominal cavity. Therefore, the study showed the exciting potential of LHRH conjugated AuNPs to target ovarian cancer and also as a potential contrast agent for novel SPCCT imaging technology.

Spectral Photon-Counting CT Imaging of Gold Nanoparticle Labelled Monocytes for Detection of Atherosclerosis: A Preclinical Study.

A key process in the development of atherosclerotic plaques is the recruitment of monocytes into the artery wall. Using spectral photon-counting computed tomography we examine whether monocyte deposition within the artery wall of ApoE-/- mouse can be detected. Primary mouse monocytes were labelled by incubating them with 15 nm gold nanoparticles coated with 11-mercaptoundecanoic acid The monocyte uptake of the particle was confirmed by electron microscopy of the cells before injection into 6-week-old apolipoprotein E deficient (ApoE-/-) mouse that had been fed with the Western diet for 10 weeks. Four days following injection, the mouse was sacrificed and imaged using a MARS spectral photon counting computed tomography scanner with a spectral range of 7 to 120 KeV with five energy bins. Imaging analysis showed the presence of X-ray dense material within the mouse aortic arch which was consistent with the spectral characteristic of gold rather than calcium. The imaging is interpreted as showing the deposition of gold nanoparticles containing monocytes within the mouse aorta. The results of our study determined that spectral photon-counting computed tomography could provide quantitative information about gold nanoparticles labelled monocytes in voxels of 90 × 90 × 90 µm3. The imaging was consistent with previous micro-CT and electron microscopy of mice using the same nanoparticles. This study demonstrates that spectral photon-counting computed tomography, using a MARS small bore scanner, can detect a fundamental atherogenic process within mouse models of atherogenesis. The present study demonstrates the feasibility of spectral photon-counting computed tomography as an emerging molecular imaging modality to detect atherosclerotic disease.

Hitchhiking probiotic vectors to deliver ultra-small hafnia nanoparticles for 'Color' gastrointestinal tract photon counting X-ray imaging.

Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO2) (∼1-2 nm) nanoparticles. The minute-made synthesis of these nanoparticles is accomplished through a simple reduction reaction. These nanoparticles were incubated with probiotic bacteria with potential health benefits and were non-specifically taken up due to their small size. Subsequently, the bacteria were lyophilized and packed into a capsule to be administered orally as the radiopaque contrast agents for delineating the GI features. These nano-bio-hybrid entities could successfully be utilized as contrast agents in vivo in the conventional and multispectral computed tomography (CT). We demonstrated in 'color' the accumulated nanoparticles using advanced detectors of the photon counting CT. The enhanced nano-bio-interfacing capability achieved here can circumvent traditional nanoparticle solubility and delivery problems while offering a patient friendly approach for GI imaging to replace the currently practiced barium meal.

Spectral Photon-Counting Molecular Imaging for Quantification of Monoclonal Antibody-Conjugated Gold Nanoparticles Targeted to Lymphoma and Breast Cancer: An In Vitro Study.

The purpose of the present study was to demonstrate an in vitro proof of principle that spectral photon-counting CT can measure gold-labelled specific antibodies targeted to specific cancer cells. A crossover study was performed with Raji lymphoma cancer cells and HER2-positive SKBR3 breast cancer cells using a MARS spectral CT scanner. Raji cells were incubated with monoclonal antibody-labelled gold, rituximab (specific antibody to Raji cells), and trastuzumab (as a control); HER2-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab (specific antibody to HER2-positive cancer cells), and rituximab (as a control). The calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT. Spectral imaging results showed that the Raji cells-rituximab-gold and HER2-positive cells-trastuzumab-gold had a quantifiable amount of gold, 5.97 mg and 0.78 mg, respectively. In contrast, both cell lines incubated with control antibody-labelled gold nanoparticles had less gold attached (1.22 mg and 0.15 mg, respectively). These results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify specific monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. The present study reports the future potential of spectral molecular imaging in detecting tumour heterogeneity so that treatment can be tuned accordingly, leading to more effective personalised medicine.