Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors (original) (raw)
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Nanomedicine (London, England), 2016
Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer. In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles. Human PC3 xenograft tumor models were used to determine CT enhancement and radiation modulating effects in vivo. Cells exposed to nanoparticles and radiation observed significant additional reduction in survival compared with radiation only. Au@DTDTPA produced a CT enhancement of 10% and a significant extension in tumor growth delay from 16.9 days to 38.3 compared with radiation only. This study demonstrates the potential of Au@DTDTPA to enhance CT-image contrast and simultaneously increases the radiosensitivity of prostate tumors.
Translational oncology, 2013
Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter "P-GNPs") as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser(139)) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1....
Targeted nanoparticles for tumour radiotherapy enhancement-the long dawn of a golden era?
Annals of translational medicine, 2016
Despite considerable progress in (I) our understanding of the aetiopathology of head and neck cancer and (II) the precise delivery of radiotherapy, long-term survival rates for many patients with head and neck cancer remain disappointingly low. Over the past years, gold nanoparticles (NP) have emerged as promising radiation dose enhancers. In a recent study published in Nanoscale, Popovtzer et al. have used gold NP coated with an antibody against the epidermal growth factor receptor (EGFR) in an attempt to enhance radiation-induced tumour cell killing in a head and neck cancer xenograft model. They report a significant impact of the combined treatment with radiation and gold NP on tumour growth and suggest an involvement of apoptosis, inhibition of angiogenesis and diminished tissue repair. In this perspective, we illustrate the underlying radiobiophysical concepts and discuss some of the challenges associated with this and related nanoparticle-radiotherapy studies from a physics, c...
Gold nanoparticles for cancer radiotherapy: a review
Cancer Nanotechnology, 2016
Background Cancer is one of the leading causes of death worldwide and the number of cancer-diagnosed patients is rapidly increasing, in part due to an ageing population, and is expected to reach 22 million cases in the next two decades (Stewart 2015). Currently, the main therapeutic approaches used to treat cancer are surgery, chemotherapy, and radiotherapy, delivered separately or in various combinations (Sánchez-Santos 2012). Surgery and radiotherapy are key players for treating primary non-metastasised solid tumours, but for patients with co-morbidities that are unfit for surgery, deep-seated tumours, especially those associated with major blood vessels, or brain tumours, combined chemotherapy approaches are common.
Hollow Gold Nanoparticals as Biocompatible Radiosensitizer: An In Vitro Proof of Concept Study
Journal of Nano Research, 2015
We report in vitro studies on radiotherapy enhancement of hollow gold nanoparticles (HAuNPs), which feature a 50 nm hollow core and a 30 nm thick polycrystalline shell. A clonogenic cell survival assay was used to assess radiation dose enhancement on breast cancer MDA-MB-231 cells. Cells were cultured in a cell culture solution in which pegylated HAuNPs were added. No cytotoxicity of the HAuNPs was observed at the nanoparticle concentration up to 4.25×10 9 nanoparticles/ml (350 µM Au concentration). A small animal X-ray irradiator and a clinical linear accelerator were used to irradiate HAuNP-treated and control groups. It shows that the radiation damage to the cells is significantly enhanced when the cells are exposed to HAuNPs. This is the first time that AuNPs with diameter larger than 100 nm has been studied for their radiosensitizing effects. In clinical settings, we envision that HAuNPs could be intratumorally injected into tumors, which is more realistic for practical usage of AuNPs as radiosensitizer than passive accumulation in tumors using the enhanced permeability and retention effect or active targeting. Larger particles are favored for the intratumoral injection approach since larger particles tend to be retained in the injection sites, and are less likely to diffuse into surrounding normal tissues. So, this proof-of-concept evaluation shows a promising potential to use HAuNPs as radiation therapy sensitizer for cancers.
Nanoparticles in radiation oncology: From bench-side to bedside
Cancer letters, 2016
Nanoparticles (NP) are "in vogue" in medical research. Pre-clinical studies accumulate evidence of NP enhancing radiation therapy. On one hand, NP, selected for their intrinsic physicochemical characteristics, are radio-sensitizers. Thus, when NP accumulate in cancer cells, they increase the radiation absorption coefficient specifically in tumour tissue, sparing healthy surrounding tissue from toxicity. On the other hand, NP, by being drug vectors, can carry radio-sensitizer therapeutics to cancer cells. Finally, NP present theranostic effects. Indeed they are used in imaging as contrast agents. NP therefore can be multi-tasking and have promising prospect in radiotherapy field. In spite of the numerous encouraging preclinical evidence, the very small number of clinical trials investigating NP possible involvement in the radiotherapy clinical practice suggests a physicians' unwillingness. Many prerequisites seem necessary including define biological mechanisms of NP ra...
Gold nanoparticles and their alternatives for radiation therapy enhancement
Frontiers in Chemistry, 2014
Radiation therapy is one of the most commonly used treatments for cancer. The dose of delivered ionizing radiation can be amplified by the presence of high-Z materials via an enhancement of the photoelectric effect; the most widely studied material is gold (atomic number 79). However, a large amount is needed to obtain a significant dose enhancement, presenting a challenge for delivery. In order to make this technique of broader applicability, the gold must be targeted, or alternative formulations developed that do not rely solely on the photoelectric effect. One possible approach is to excite scintillating nanoparticles with ionizing radiation, and then exploit energy transfer between these particles and attached dyes in a manner analogous to photodynamic therapy (PDT). Doped rare-earth halides and semiconductor quantum dots have been investigated for this purpose. However, although the spectrum of emitted light after radiation excitation is usually similar to that seen with light excitation, the yield is not. Measurement of scintillation yields is challenging, and in many cases has been done only for bulk materials, with little understanding of how the principles translate to the nanoscale. Another alternative is to use local heating using gold or iron, followed by application of ionizing radiation. Hyperthermia pre-sensitizes the tumors, leading to an improved response. Another approach is to use chemotherapeutic drugs that can radiosensitize tumors. Drugs may be attached to high-Z nanoparticles or encapsulated. This article discusses each of these techniques, giving an overview of the current state of nanoparticle-assisted radiation therapy and future directions.
Targeted radiotherapy with gold nanoparticles: current status and future perspectives
Nanomedicine, 2014
Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clini...
Functionalized radioactive gold nanoparticles in tumor therapy
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2011
The development of new treatment modalities that offer clinicians the ability to reduce sizes of tumor prior to surgical resection or to achieve complete ablation without surgery would be a significant medical breakthrough in the overall care and treatment of prostate cancer patients. The goal of our investigation is aimed at validating the hypothesis that Gum Arabic-functionalized radioactive gold nanoparticles (GA-198 AuNP) have high affinity toward tumor vasculature. We hypothesized further that intratumoral delivery of the GA-198 AuNP agent within prostate tumor will allow optimal therapeutic payload that will significantly or completely ablate tumor without side effects, in patients with hormone refractory prostate cancer. In order to evaluate the therapeutic efficacy of this new nanoceutical, AuNP was produced by stabilization of radioactive gold nanoparticles ( 198 Au) with the FDA-approved glycoprotein, GA. This review will describe basic and clinical translation studies toward realization of the therapeutic potential and myriad of clinical applications of GA-198 AuNP agent in treating prostate and various solid tumors in human cancer patients.