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

Ostadhossein, Fatemeh; Moitra, Parikshit; Gunaseelan, Nivetha; Nelappana, Michael; Lowe, Chiara; Moghiseh, Mahdieh; Butler, Anthony; Ruiter, Niels de; Mandalika, H; Tripathi, Indu; Misra, Santosh K.; Pan, Dipanjan

doi:10.1039/d1nh00626f

Cited by 20 publications

(14 citation statements)

References 71 publications

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“…To some extent this is related to the biological relevance of iron oxide and its incompatibility with NMR spectroscopy. However, hafnium oxide is also a valuable nanocrystal for biomedicine, − and it is compatible with NMR. This is currently the focus in our own research group.…”

Section: Discussionmentioning

confidence: 99%

The Surface Chemistry of Colloidal Nanocrystals Capped by Organic Ligands

Roo

2023

Chem. Mater.

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Nanocrystal surface chemistry is a pivotal element in the synthesis and application of nanocrystals. This perspective focuses on colloidal nanocrystals, capped with organic ligands. We start with insights into a workhorse characterization technique: solution nuclear magnetic resonance (NMR) spectroscopy. We then discuss the different models used to conceptualize nanocrystal surface chemistry and how the classification of binding motifs helps in the prediction of surface reactions. The thermodynamics and kinetics of these surface reactions are analyzed, and we arrive at the deciding factors for a high binding affinity: sterics, pK a/pK b, and solubility/solvent. Finally, we discuss recent ligand designs; most notably we introduce a new ligand class: monoalkyl phosphinic acids.

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Section: Discussionmentioning

confidence: 99%

The Surface Chemistry of Colloidal Nanocrystals Capped by Organic Ligands

Roo

2023

Chem. Mater.

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“…15,16,70,103,122,123 Spherical hafnia nanoparticles with diameters below 100 nm are most commonly studied for medical applications. [5][6][7][8]21,76 Other reported morphologies for hafnium-based therapeutic agents include mesoporous spherical structures (130 nm), 38 rods (40 × 100 nm), 87 and ellipsoids (40−400 nm). 124 Sahraneshin et al 29 demonstrated the influence of reaction temperature on shape during hydrothermal synthesis and prepared trapezohedron (16 nm) and oval (16 nm) shaped hafnia particles.…”

Section: Characterization and Morphologymentioning

confidence: 99%

“…Stringent histopathology studies illustrated a high level of safety and lack of toxicity from the particles. In a separate published work, 7 this group prepared a hafnia-based contrast agent targeted for the gastrointestinal tract. Targeting was accomplished via microencapsulation of ultrasmall hafnia particles within a probiotic system.…”

Section: Applications In Imagingmentioning

confidence: 99%

“…This ultimately results in opportunities for lower doses and less harmful side effects. Using a similar concept and approach, hafnium-based nanoparticles have also been utilized in radiation-based imaging such as X-ray and CT as the greater interaction probability provides a platform for targeted contrast. − Additionally, other relevant possibilities include particle functionalization as drug delivery platforms and numerous avenues for physical and active targeting. As recent strides in nanomedicine have demonstrated effective clinical application and other research efforts lend support to complementary improvements, it is evident that the further progression can enable contemporary solutions to existing and future obstacles in medicine.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Bioapplication of Emerging Nanomaterials of Hafnium

Skrodzki,

Molinaro,

Brown

et al. 2024

ACS Nano

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A significant amount of progress in nanotechnology has been made due to the development of engineered nanoparticles. The use of metallic nanoparticles for various biomedical applications has been extensively investigated. Biomedical research is highly focused on them because of their inert nature, nanoscale structure, and similar size to many biological molecules. The intrinsic characteristics of these particles, including electronic, optical, physicochemical, and surface plasmon resonance, that can be altered by altering their size, shape, environment, aspect ratio, ease of synthesis, and functionalization properties, have led to numerous biomedical applications. Targeted drug delivery, sensing, photothermal and photodynamic therapy, and imaging are some of these. The promising clinical results of NBTXR3, a high-Z radiosensitizing nanomaterial derived from hafnium, have demonstrated translational potential of this metal. This radiosensitization approach leverages the dependence of energy attenuation on atomic number to enhance energy−matter interactions conducive to radiation therapy. High-Z nanoparticle localization in tumor issue differentially increases the effect of ionizing radiation on cancer cells versus nearby healthy ones and mitigates adverse effects by reducing the overall radiation burden. This principle enables material multifunctionality as contrast agents in X-ray-based imaging. The physiochemical properties of hafnium (Z = 72) are particularly advantageous for these applications. A well-placed K-edge absorption energy and high mass attenuation coefficient compared to elements in human tissue across clinical energy ranges leads to significant attenuation. Chemical reactivity allows for variety in nanoparticle synthesis, composition, and functionalization. Nanoparticles such as hafnium oxide exhibit excellent biocompatibility due to physiochemical inertness prior to incidence with ionizing radiation. Additionally, the optical and electronic properties are applicable in biosensing, optical component coatings, and semiconductors. The wide interest has prompted extensive research in design and synthesis to facilitate property fine-tuning. This review summarizes synthetic methods for hafnium-based nanomaterials and applications in therapy, imaging, and biosensing with a mechanistic focus. A discussion and future perspective section highlights clinical progress and elaborates on current challenges. By focusing on factors impacting applicational effectiveness and examining limitations this review aims to support researchers and expedite clinical translation of future hafnium-based nanomedicine.

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“…Hafnium oxide exhibits strong contrast enhancement in conventional radiography and CT due to its high density, favorable K-edge, and the high atomic number of the metal . HfO 2 nanocrystals are biocompatible ,, and have already seen clinical use as a radiotherapy enhancer. , As a diagnostic contrast agent, cationic HfO 2 nanocrystals exposed bone-microdamage in vivo , and using probiotic vectors HfO 2 nanocrystals allowed imaging the gastrointestinal tract . While multimodal imaging probes for other oxides such as iron oxide nanoparticles have been developed, − none are currently available for HfO 2 nanocrystals.…”

Section: Introductionmentioning

confidence: 99%

Dual-Modality Hafnium Oxide Nanocrystals for in Vivo Computed Tomography and Fluorescence Imaging of Sentinel Lymph Nodes

Deblock,

Descamps,

Goemaere

et al. 2023

Chem. Mater.

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In the surgical treatment of breast cancer, the primary tumor is removed together with the sentinel lymph nodes (SLNs). Current clinical procedures involve radioactive compounds (exposing both patient and surgeon) and blue dyes, which often induce long-lasting skin discoloration. Here, we demonstrate the in vivo detection of SLNs in mice using X-ray computed tomography (CT) and near-infrared fluorescence via a dual-modality imaging probe. CT contrast is provided by hafnium oxide nanocrystals, stabilized in physiological buffer using custom designed nitrocatechol ligands. IRDye 800CW is covalently attached to the nanocrystal surface to impart surgery-compatible fluorescence with a high penetration depth. The well-controlled surface functionalization is assessed by 1 H NMR spectroscopy, confirming the tight binding of the ligands. During a longitudinal in vivo study the sentinel node is successfully and selectively detected via both imaging modalities 15−30 min postinjection of the probe, allowing for preoperative SLN mapping with X-ray CT and intraoperative removal using fluorescence-guided surgery. Our imaging probe features the correct lymphatic drainage while utilizing fast, economical, and readily available imaging infrastructure, without the need for nuclear medicine or staining molecules.

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

Abstract: Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of the contrast agents and drugs mediated by the nanoparticles due to its harsh environment. Herein, we...

Cited by 20 publications

References 71 publications

The Surface Chemistry of Colloidal Nanocrystals Capped by Organic Ligands

The Surface Chemistry of Colloidal Nanocrystals Capped by Organic Ligands

Synthesis and Bioapplication of Emerging Nanomaterials of Hafnium

Dual-Modality Hafnium Oxide Nanocrystals for in Vivo Computed Tomography and Fluorescence Imaging of Sentinel Lymph Nodes

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