Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy.

Published on Feb 1, 2020in British Journal of Radiology2.196
· DOI :10.1259/BJR.20190742
Aaron Bannister3
Estimated H-index: 3
(UVic: University of Victoria),
Kyle Bromma7
Estimated H-index: 7
(UVic: University of Victoria)
+ 6 AuthorsDevika B. Chithrani17
Estimated H-index: 17
Sources
Abstract
Objective:One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizi...
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Objective: The incorporation of high atomic number materials such as gold nanoparticles (GNPs) into tumor cells is being tested to enhance the local radiotherapy (RT) dose. It is also known that th...
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Combined use of chemotherapy and radiation therapy is commonly used in cancer treatment, but the toxic effects on normal tissue are a major limitation. This study assesses the potential to improve radiation therapy when combining gold nanoparticle (GNP) mediated radiation sensitization with chemoradiation compared to chemoradiation alone. Incorporation of GNPs with 2 Gy, 6 MV (megavoltage) radiation resulted in a 19 ± 6% decrease in survival of MDA-MB-231 cells. Monte-Carlo simulations were perf...
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: Exposure to ionizing radiation (IR) induces various types of DNA damage, of which DNA double-strand breaks are the most severe, leading to genomic instability, tumorigenesis, and cell death. Hence, cells have developed DNA damage responses and repair mechanisms. IR also causes the accumulation of endogenous reactive oxidative species (ROS) in the irradiated cells. Upon exposure to low-dose irradiation, the IR-induced biological effects mediated by ROS were relatively more significant than thos...
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Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo mod...
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Abstract An efficient surface engineering strategy for MnO nanoparticles was developed to attain enhanced colloidal stability, selective uptake by and toxicity to specific cancer cells. Specifically, MnO nanoclusters prepared by polyol method were grafted with polyglycerol (MnO-PG), and then conjugated with arginine-glycine-aspartate peptide (MnO-PG-RGD) through stepwise organic reactions. The physicochemical properties of the surface engineered MnO nanoclusters were characterized by powder X-ra...
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In recent decades neoadjuvant therapies such as combined chemotherapy and radiotherapy have been introduced for cancer management. Compared with monotherapy modalities, neoadjuvant therapy is associated with greater effectiveness while having minor side effects. Docetaxel is a chemotherapy agent for breast cancer treatment which can blocks the cell cycle at the G2/M phase which has shown special sensitivity to the ionizing radiation and hence causes cell death. To the best of our knowledge, ther...
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Purpose To evaluate whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathologic complete response (pCR) to treatment for locally advanced breast cancer (LABC). Methods and Materials This prospective phase 2 trial recruited 32 LABC patients from 2009 to 2011. Patients received neoadjuvant every-3-weekly 5-fluorouracil (500 mg/m 2 ), epirubicin (100 mg/m 2 ), and cyclophosphamide (500 mg/m 2 ) for 3 cycles, followed by weekly docetaxel (35 mg/m 2 ) for 9 c...
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The interaction of nanoparticles intracellularly has been investigated widely but the mechanisms of such interactions are not fully understood. Here, the authors utilize a semi-quantitative technique to assess the intracellular transportation and clustering potential of nanoparticles in real-time.
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The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA...
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About half of cancer patients (50%) receive radiotherapy (RT) for the treatment of local tumors. However, one of the main obstacles in RT is the close proximity of adjacent organs at risk, resulting in treatment doses being limited by significant tissue toxicity, hence preventing the necessary dose escalation that would guarantee local control. Effective local cancer therapy is needed to avoid progression of tumors and to decrease the development of systemic metastases which may further increase...
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Radiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials, such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor environment compared ...
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Abstract Radionuclides have been widely used for multimodal imaging and radioisotope therapy of cancer. Various nanomaterials have been developed as excellent nanocarriers of radionuclides for the targeted delivery into tumors, in order to minimize the unnecessary side effect and enhance the therapeutic efficacy of radiotherapy. Among those nanomaterials, gold nanomaterials with tunable morphologies, easy modification, good biological safety, and radiation sensitization capability are excellent ...
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According to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxi...
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Successful integration of nanotechnology into the current paradigm of cancer therapy requires proper understanding of the interface between nanoparticles (NPs) and cancer cells, as well as other key components within the tumor microenvironment (TME), such as normal fibroblasts (FBs) and cancer-associated FBs (CAFs). So far, much focus has been on cancer cells, but FBs and CAFs also play a critical role: FBs suppress the tumor growth while CAFs promote it. It is not yet known how NPs interact wit...
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One of the major issues in cancer radiotherapy (RT) is normal tissue toxicity. Introduction of radiosensitizers like gold nanoparticles (GNPs) into cancer cells to enhance the local RT dose has been tested successfully. However, it is not known how GNPs interact with other stromal cells such as normal fibroblasts (FBs) and cancer associated fibroblasts (CAFs) within the tumour microenvironment. It is known that FBs turn into CAFs to promote tumour growth. Hence, we used FBs and CAFs along with H...
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Nanoparticles (NPs) have shown promise in both radiotherapy and chemotherapy. NPs are mainly transported along cellular microtubules (MTs). Docetaxel (DTX) is a commonly used chemotherapeutic drug that can manipulate the cellular MT network to maximize its clinical benefit. However, the effect of DTX on NP behaviour has not yet been fully elucidated. We used gold NPs of diameters 15 and 50 nm at a concentration of 0.2 nM to investigate the size dependence of NP behaviour. Meanwhile, DTX concentr...
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