Enhancing Colorectal Cancer Radiation Therapy Efficacy using Silver Nanoprisms Decorated with Graphene as Radiosensitizers

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Abstract

Metal nanoparticles have significant interaction cross-sections with electromagnetic waves due to their large surface area-to-volume ratio, which can be exploited in cancer radiotherapy to locally enhance the radiation dose deposition in tumors. We developed a new type of silver nanoparticle composite, PEGylated graphene quantum dot (GQD)-decorated Silver Nanoprisms (pGAgNPs), that show excellent in vitro intracellular uptake and radiosensitization in radiation-sensitive HCT116 and relatively radiation-resistant HT29 colorectal cancer cells. Furthermore, following biodistribution analysis of intravenously injected nanoparticles in nude mice bearing HCT116 tumors radiosensitization was evaluated. Treatment with nanoparticles and a single radiation dose of 10 Gy significantly reduces the growth of colorectal tumors and increases the survival time as compared to treatment with radiation only. Our findings suggest that these novel nanoparticles offer a promising paradigm for enhancing colorectal cancer radiation therapy efficacy.

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Most cited references 37

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Nanoparticle Uptake: The Phagocyte Problem.

Heather Herd Gustafson, Dolly Holt-Casper, David Grainger … (2015)

Phagocytes are key cellular participants determining important aspects of host exposure to nanomaterials, initiating clearance, biodistribution and the tenuous balance between host tolerance and adverse nanotoxicity. Macrophages in particular are believed to be among the first and primary cell types that process nanoparticles, mediating host inflammatory and immunological biological responses. These processes occur ubiquitously throughout tissues where nanomaterials are present, including the host mononuclear phagocytic system (MPS) residents in dedicated host filtration organs (i.e., liver, kidney spleen, and lung). Thus, to understand nanomaterials exposure risks it is critical to understand how nanomaterials are recognized, internalized, trafficked and distributed within diverse types of host macrophages and how possible cell-based reactions resulting from nanomaterial exposures further inflammatory host responses in vivo. This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.

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James Hainfeld, Daniel N. Slatkin, Henry Smilowitz (2004)

Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight), which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal-tissue gold concentration ratios remained approximately 8:1 during several minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x-rays alone and 0% with gold alone. The increase in tumours safely ablated was dependent on the amount of gold injected. The gold nanoparticles were apparently non-toxic to mice and were largely cleared from the body through the kidneys. This novel use of small gold nanoparticles permitted achievement of the high metal content in tumours necessary for significant high-Z radioenhancement.

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A systematic study of the synthesis of silver nanoplates: is citrate a "magic" reagent?

Qiao Zhang, Na Li, James Goebl … (2011)

In this work we have carried out systematic studies and identified the critical role of hydrogen peroxide instead of the generally believed citrate in the well-known chemical reduction route to silver nanoplates. This improved understanding allows us to develop consistently reproducible processes for the synthesis of nanoplates with high efficiency and yields. By harnessing the oxidative power of H(2)O(2), various silver sources including silver salts and metallic silver can be directly converted to nanoplates with the assistance of an appropriate capping ligand, thus significantly enhancing the reproducibility of the synthesis. Contrary to the previous conclusion that citrate is the key component, we have determined that the group of ligands with selective adhesion to Ag (111) facets can be expanded to many di- and tricarboxylate compounds whose two nearest carboxylate groups are separated by two or three carbon atoms. We have also found that the widely used secondary ligand polyvinylpyrrolidone can be replaced by many hydroxyl group-containing compounds or even removed entirely while still producing nanoplates of excellent uniformity and stability. In addition to the general understanding of NaBH(4) as a reducing agent, it has also been found to act as a capping agent to stabilize the silver nanoparticles, prolong the initiation time required for nanoplate nucleation, and contribute to the control of the thickness as well as the aspect ratio of silver nanoplates. The improved insight into the specific roles of the reaction components and significantly enhanced reproducibility are expected to help elucidate the formation mechanism of this interesting nanostructure.

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Author and article information

Contributors

Khaled Habiba: khabiba@gmail.com

Sunil Krishnan: krishnan.sunil@mayo.edu

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 19 November 2019

Publication date PMC-release: 19 November 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 17120

Affiliations

[1 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Radiation Oncology, , The University of Texas MD Anderson Cancer Center, ; Houston, TX 77030 USA

[2 ]GRID grid.280412.d, Department of Biology, , University of Puerto Rico -Rio Piedras Campus, ; San Juan, PR 00925-2537 USA

[3 ]ISNI 0000 0004 0462 1680, GRID grid.267033.3, Molecular Sciences Research Center, , University of Puerto Rico, ; San Juan, Puerto Rico 00926-2614 USA

[4 ]GRID grid.280412.d, Department of Physics, , University of Puerto Rico -Rio Piedras Campus, ; San Juan, PR 00925-2537 USA

[5 ]GRID grid.280412.d, Department of Chemistry, , University of Puerto Rico -Rio Piedras Campus, ; San Juan, PR 00925-2537 USA

[6 ]ISNI 0000 0004 0462 1680, GRID grid.267033.3, Comprehensive Cancer Center, , University of Puerto Rico, ; San Juan, PR 00936-3027 USA

[7 ]ISNI 0000 0004 0443 9942, GRID grid.417467.7, Present Address: Department of Radiation Oncology, , Mayo Clinic Florida, ; Jacksonville, FL 32224 USA

Author information

Vladimir Makarov http://orcid.org/0000-0003-1813-1837

Article

Publisher ID: 53706

DOI: 10.1038/s41598-019-53706-0

PMC ID: 6864075

PubMed ID: 31745177

SO-VID: 956458c4-500c-4212-b596-938233f1cb72

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 19 August 2019

Date accepted : 5 November 2019

Funding

Funded by: FundRef https://doi.org/10.13039/100000054, U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI);

Award ID: NIH U54 CA096297/CA096300

Award ID: P30 CA16672

Award ID: NIH U54 CA096297/CA096300

Award ID: P30 CA16672

Award Recipient : Khaled Habiba Brad R. Weiner Sunil Krishnan

Funded by: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

Funded by: FundRef https://doi.org/10.13039/100005759, Puerto Rico Space Grant Consortium (NASA Puerto Rico Space Grant Consortium);

Award ID: NNX15AK43A

Award ID: NNX15AI11H

Award ID: NNX15AK43A

Award ID: NNX15AI11H

Award ID: NNX15AK43A

Award ID: NNX15AI11H

Award Recipient : Vladimir Makarov Brad R. Weiner Gerardo Morell

Funded by: FundRef https://doi.org/10.13039/100006194, NASA | Kennedy Space Center (KSC, Inc.);

Award ID: 80NSSC19M0049

Award Recipient : Vladimir Makarov Brad R. Weiner Gerardo Morell

Funded by: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

Funded by: John E. and Dorothy J. Harris endowed professorship

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ScienceOpen disciplines: Uncategorized

Keywords: nanostructures,nanotechnology in cancer

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ScienceOpen disciplines: Uncategorized

Keywords: nanostructures, nanotechnology in cancer

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Enhancing Colorectal Cancer Radiation Therapy Efficacy using Silver Nanoprisms Decorated with Graphene as Radiosensitizers

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Most cited references 37

Nanoparticle Uptake: The Phagocyte Problem.

The use of gold nanoparticles to enhance radiotherapy in mice.

A systematic study of the synthesis of silver nanoplates: is citrate a "magic" reagent?

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