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Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

ABSTRACT: Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7°C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results show the feasibility of using a single nanostructure for image-guided local tumor PTA therapy with photoacoustic molecular imaging.

SUBMITTER: Lu W

PROVIDER: S-EPMC3185126 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

Lu Wei W Melancon Marites P MP Xiong Chiyi C Huang Qian Q Elliott Andrew A Song Shaoli S Zhang Rui R Flores Leo G LG Gelovani Juri G JG Wang Lihong V LV Ku Geng G Stafford R Jason RJ Li Chun C

Cancer research 20110819 19

Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and a ...[more]

PMID: 21856744

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Project description:Purpose To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS) mixed with ethiodized oil for improved photothermal ablation (PTA)-chemoembolization therapy (CET) of hepatocellular carcinoma (HCC) in rats. Materials and Methods Animal experiments were approved by the institutional animal care and use committee and performed from February 2014 to April 2015. Male Sprague-Dawley rats (n = 45; age, 12 weeks) were inoculated with N1S1 HCC cells in the liver, and 8 days later, were randomly divided into two groups of 10 rats. Group 1 rats received intrahepatic arterial injection of PEG-HAuNS and ethiodized oil alone; group 2 received pretreatment with CA4P and injection of PEG-HAuNS and ethiodized oil 5 minutes later. The gold content of tumor and liver tissue at 1 hour or 24 hours after injection was quantified by using neutron activation analysis (n = 5 per time point). Five rats received pretreatment CA4P, PEG-copper 64-HAuNS, and ethiodized oil and underwent micro-positron emission tomography (PET)/computed tomography (CT). In a separate study, three groups of six rats with HCC were injected with saline solution (control group); CA4P, Dox-loaded PEG-coated HAuNS (Dox@PEG-HAuNS), and ethiodized oil (CET group); or CA4P, Dox@PEG-HAuNS, ethiodized oil, and near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified at postmortem histopathologic and/or autoradiographic examination. Wilcoxon rank-sum test and Pearson correlation analyses were performed. Results PEG-HAuNS uptake in CA4P-pretreated HCC tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 hour (P < .03) and 24 hours (P < .01). Mean ± standard deviation of tumor-to-liver PEG-HAuNS uptake ratios at 1 hour and 24 hours, respectively, were 5.63 ± 3.09 and 1.68 ± 0.77 in the CA4P-treated group and 1.29 ± 2.40 and 0.14 ± 0.11 in the non-CA4P-treated group. Micro-PET/CT allowed clear delineation of tumors, enabling quantitative imaging analysis. Laser irradiation increased temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Mean HCC tumor volumes 10 days after therapy were 1.68 cm3 ± 1.01, 3.96 cm3 ± 1.75, and 6.13 cm3 ± 2.27 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P < .05). Conclusion CA4P pretreatment caused a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the efficacy of anti-HCC treatment with PTA-CET in rats. © RSNA, 2016 Online supplemental material is available for this article.

Project description:Radiotherapy is preferred to chemotherapy as an adjuvant therapy for postoperative cervical cancer owing to its convenience and minimal effects on various non-targeted systems. The present study sought to investigate whether the utilization of anti-MET proto-oncogene, receptor tyrosine kinase (c-Met) antibodies conjugated to hollow gold nanospheres (anti-c-Met/HGNs) may enhance the efficiency of radiation therapy for cervical cancer. Anti-c-Met/HGNs were synthesized and confirmed to target c-Met, which was overexpressed on the cell membrane of multiple malignancies. The successful synthesis of HGNs was observed using transmission electron microscopy (TEM). Overrepresentation of c-Met in the human cervical cancer cell line CaSki was verified by immunofluorescence. The cellular uptake of HGNs was assessed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). To assess the toxicity of functionalized gold nanospheres, a cell proliferation and toxicity assay was used and flow cytometry, with staining by propidium iodide (PI), was performed to study the cell cycle changes. Each experiment was conducted on three groups: Control, HGNs alone and anti-c-Met/HGNs, with each group also assessed with or without X-rays. The variation of apoptotic rate was observed by flow cytometry using a dual-staining Annexin V-fluorescein isothiocyanate/PI kit. Expression of apoptosis-associated proteins was examined by western blot analysis. TEM revealed a number of hollow spheres with cells with an average diameter of 56.25 nm and a mean wall thickness of 6.56 nm. CaSki cells were detected by inverted fluorescence microscopy via a layer of fluorescent green marker, and ICP-AES confirmed the distinct uptake of anti-c-Met/HGNs by each CaSki cell. Anti-c-Met/HGNs induced 38.7% of cells to stay in the G2/M phase, whereas the equivalent proportion in the control group was 19.8%. Compared with other groups, CaSki cells treated with anti-c-Met/HGNs and 5 Gy X-ray radiation exhibited a higher apoptosis rate (16.92%) and a higher early apoptotic rate (12.30%) compared with cells under other conditions (control+0 Gy: 3.16 and 1.69%; HGN+0 Gy: 3.98 and 1.94%; anti-c-Met/HGN+0 Gy: 3,47 and 1.85%; control+5 Gy: 5.35 and 3.66%; HGN+5 Gy: 7.91 and 4.06%). The anti-c-Met/HGN X-ray-treated group also evidently overexpressed caspase-3 and BCL2 associated X, apoptosis regulator. Anti-c-Met/HGN may, therefore, aid the sensitivity of radiation therapy in cervical cancer.

Dataset Information

Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

Publications

Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

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