Intratumoral Gold Nanoparticle-Enhanced CT Imaging: An in Vivo Investigation of Biodistribution and Retention

Terracciano, Rossana; Sprouse, Marc L.; Wang, Dennis; Ricchetti, Sara; Hirsch, Matteo; Ferrante, Nicola Di; Butler, E. Brian; Demarchi, Danilo; Grattoni, Alessandro; Filgueira, Carly S.

doi:10.1109/nano47656.2020.9183611

Cited by 12 publications

(15 citation statements)

References 11 publications

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“…This result is consistent with the increase in BSA-GNP volume over time in Figure 5 C: the more the BSA-GNPs diffuse throughout the tissues, the less they attenuate the X-rays. Citrate-GNP volume is constant over time, confirming the preliminary results we previously obtained [ 55 ]: citrate-GNPs do not diffuse over time intratumorally, but instead form a single cluster of particles. Overall, a heterogenic intratumoral distribution pattern was found for both citrate-GNPs and BSA-GNPs.…”

Section: Resultssupporting

confidence: 90%

“…We hypothesize that by controlling the adsorption of proteins on the GNP surface, we can modulate the zonal distribution of the particles in the tumor. We previously demonstrated that our spherical GNPs have a significant radio-sensitization property in vitro [ 54 ], inducing DNA damage in Lewis lung carcinoma (LLC) cells, as well as excellent properties as contrast agents for computed tomography (CT) in vivo [ 55 ]. However, these preliminary studies did not consider the hypothesis that surface protein adsorption can affect the intratumoral distribution and retention of the particles.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

et al. 2021

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The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey’s multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

et al. 2021

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show abstract

“…This result is consistent with the increase in BSA-GNP volume over time in Figure 4C: the more the BSA-GNPs diffuse throughout the tissues, the less they attenuate the X-rays. Citrate-GNP volume is constant over time, confirming the preliminary results we previously obtained [55]: citrate-GNPs do not diffuse over time intratumorally, but instead form a single cluster of particles. Overall, a heterogenic intratumoral distribution pattern was found for both citrate-GNPs and BSA-GNPs.…”

Section: In Vivo Biodistribution and Retention Of Gnpssupporting

confidence: 89%

“…We hypothesize that by controlling the adsorption of proteins on the GNP surface, we can modulate the zonal distribution of the particles in the tumor. We previously demonstrated that our spherical GNPs have a significant radiosensitization nature in vitro [54], inducing DNA damage in Lewis Lung Carcinoma (LLC) cells as well as excellent properties as contrast agents for Computed Tomography (CT) in vivo [55]. However, these preliminary studies didn't consider the hypothesis that surface protein adsorption can affect intratumoral distribution and retention of the particles.…”

Section: Introductionmentioning

confidence: 97%

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Terracciano

Zhang

Butler

et al. 2020

Preprint

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Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high resolution Computed Tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis Lung Carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate stabilized or passivated with Bovine Serum Albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n=8 mice/group). Significant difference is highlighted between citrate-GNP and BSA-GNP groups (**p < 0.005, Tukey’s multiple comparisons test), confirming the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo highlighting the spatial heterogeneity of the solid tumor.

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“…Therefore, Au NPs are broadly used in many biological applications, particularly in medical and gene therapy [ 22 ]. Importantly, Au NPs may be applied as biosensors or vessels for drug delivery and even selective treatment of cancer [ 27 , 28 , 29 ]. According to the literature, Au NPs have been reported as effectual antibacterial agents against antibiotic-resistant strains, such as S. aureus, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Salmonella typhimurium, Shigella dysenteriae , Vibrio cholerae and Mycobacterium tuberculosis [ 21 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains

et al. 2021

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Background: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. Methods: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. Results: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. Conclusions: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria.

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Intratumoral Gold Nanoparticle-Enhanced CT Imaging: An in Vivo Investigation of Biodistribution and Retention

Cited by 12 publications

References 11 publications

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains

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