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Third generation gold nanoplatform optimized for radiation therapy.

ABSTRACT: We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRad™) optimized for applications in radiation therapy. The AuRad™ nanoplatform has the following key features: (I) surface coating of hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile nanoplatform to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is optimized for longer circulation, higher tumor uptake and modulated clearance; (III) high radiation enhancement. We have synthesized ultrasmall 2-3 nm gold nanoparticles, followed by attachment of hetero-bifunctional PEG and further conjugation of fluorophore AlexaFlour 647 for optical imaging, with a stability of more than 6 months. Confocal bioimaging with HeLa cells showed robust uptake of biocompatible nanoparticles in cells. Irradiation experiments X-rays showed greater than 2.8-fold cell kill enhancement as demonstrated by clonogenic survival assays. The results indicate that AuRad nanoplatform can act as potential theranostic agent in radiation therapy.

SUBMITTER: Kumar R

PROVIDER: S-EPMC3877840 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Third generation gold nanoplatform optimized for radiation therapy.

Kumar Rajiv R Korideck Houari H Ngwa Wilfred W Berbeco Ross I RI Makrigiorgos G Mike GM Sridhar Srinivas S

Translational cancer research 20130801 4

We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRad<sup>™</sup>) optimized for applications in radiation therapy. The AuRad<sup>™</sup> nanoplatform has the following key features: (I) surface coating of hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile nanoplatform to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is optimized for long ...[more]

PMID: 24392307

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Project description:BackgroundRadiation therapy is a main treatment option for cancer. Due to normal tissue toxicity, radiosensitizers are commonly used to enhance RT. In particular, heavy metal or high-Z materials, such as gold nanoparticles, have been investigated as radiosensitizers. So far, however, the related studies have been focused on spherical gold nanoparticles. In this study, we assessed the potential of ultra-thin gold nanowires as a radiosensitizer, which is the first time.MethodsGold nanowires were synthesized by the reduction of HAuCl4 in hexane. The as-synthesized gold nanowires were then coated with a layer of PEGylated phospholipid to be rendered soluble in water. Spherical gold nanoparticles coated with the same phospholipid were also synthesized as a comparison. Gold nanowires and gold nanospheres were first tested in solutions for their ability to enhance radical production under irradiation. They were then incubated with 4T1 cells to assess whether they could elevate cell oxidative stress under irradiation. Lastly, gold nanowires and gold nanoparticles were intratumorally injected into a 4T1 xenograft model, followed by irradiation applied to tumors (3 Gy/per day for three days). Tumor growth was monitored and compared.ResultsOur studies showed that gold nanowires are superior to gold nanospheres in enhancing radical production under X-ray radiation. In vitro analysis found that the presence of gold nanowires caused elevated lipid peroxidation and intracellular oxidative stress under radiation. When tested in vivo, gold nanowires plus irradiation led to better tumor suppression than gold nanospheres plus radiation. Moreover, gold nanowires were found to be gradually reduced to shorter nanowires by glutathione, which may benefit fractionated radiation.ConclusionOur studies suggest that gold nanowires are a promising type of radiosensitizer that can be safely injected into tumors to enhance radiotherapy. While the current study was conducted in a breast cancer model, the approach can be extended to the treatment of other cancer types.

Project description:Conventional volumetric modulated arc therapy (VMAT) discretizes the angular space into equally spaced control points during planning and then optimizes the apertures and weights of the control points. The aperture at an angle in between two control points is obtained through interpolation. This approach tacitly ignores the differential need for intensity modulation of different angles. As such, multiple arcs are often required, which may oversample some angle(s) and undersample others. The purpose of this work is to develop a segmentally boosted VMAT scheme to eliminate the need for multiple arcs in VMAT treatment with improved dose distribution and∕or delivery efficiency.The essence of the new treatment scheme is how to identify the need of individual angles for intensity modulation and to provide the necessary beam intensity modulation for those beam angles that need it. We introduce a "demand metric" at each control point to decide which station or control points need intensity modulation. To boost the modulation at selected stations, additional segments are added in the vicinity of the selected stations. The added segments are then optimized together with the original set of station or control points as a whole. The authors apply the segmentally boosted planning technique to four previously treated clinical cases: two head and neck (HN) cases, one prostate case, and one liver case. The proposed planning technique is compared with conventional one-arc and two-arc VMAT.The proposed segmentally boosted VMAT technique achieves better critical structure sparing than one-arc VMAT with similar or better target coverage in all four clinical cases. The segmentally boosted VMAT also outperforms two-arc VMAT for the two complicated HN cases, yet with ∼30% reduction in the machine monitor units (MUs) relative to two-arc VMAT, which leads to less leakage∕scatter dose to the patient and can potentially translate into faster dose delivery. For the less challenging prostate and liver cases, similar critical structure sparing as the two-arc VMAT plans was obtained using the segmentally boosted VMAT. The benefit for the two simpler cases is the reduction of MUs and improvement of treatment delivery efficiency.Segmentally boosted VMAT achieves better dose conformality and∕or reduced MUs through effective consideration of the need of individual beam angles for intensity modulation. Elimination of the need for multiple arcs in rotational arc therapy while improving the dose distribution should lead to improved workflow and treatment efficacy, thus may have significant implication to radiation oncology practice.

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Third generation gold nanoplatform optimized for radiation therapy.

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Third generation gold nanoplatform optimized for radiation therapy.

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