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Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

ABSTRACT: Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I-TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the O-H bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine.

SUBMITTER: Su W

PROVIDER: S-EPMC7237849 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

Su Weiwei W Wang Han H Wang Tao T Li Xiao X Tang Zhongmin Z Zhao Shuai S Zhang Meng M Li Danni D Jiang Xingwu X Gong Teng T Yang Wei W Zuo Changjing C Wu Yelin Y Bu Wenbo W

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200406 10

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (<sup>125</sup>I) are used in situ to construct active sites in a nanocatalyst (TiO<sub>2</sub>) and the application of this method is further extended to cancer catalytic internal radiothe ...[more]

PMID: 32440481

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Project description:PURPOSE:Auger electrons emitted by radioisotopes such as 125I have a high linear energy transfer and short mean-free path in tissue (<10??m), making them suitable for treating micrometastases while sparing normal tissues. The authors developed and subsequently investigated a cancer cell-selective small molecule phospholipid ether analog to deliver 125I to triple-negative breast cancer (TNBC) cells in vivo. METHODS:A Current Good Manufacturing Practice (cGMP) method to radiolabel 125I-CLR1404 (CLR 125) with >95% radiochemical purity was established. To estimate CLR 125 in vivo dosimetry and identify dose-limiting organs, the biodistribution of the analog compound 124I-CLR1404 (CLR 124) was investigated using micro-positron emission tomography (PET)/computed tomography (CT) in conjunction with a Monte Carlo dosimetry platform to estimate CLR 125 dosimetry. In vivo antitumor efficacy was tested by injecting nude mice bearing either MDA-MB-231-luc orthotopic xenografts or lung metastases with 74?MBq (3.7 GBq/kg) of CLR 125 or an equivalent mass amount of nonradiolabeled CLR 125. Longitudinal tumor measurements using calipers and bioluminescence imaging were obtained for the xenografts and lung metastases, respectively. RESULTS:Dosimetry analysis estimated that CLR 125 would impart the largest absorbed dose to the tumor per injected activity (0.261?±?0.023 Gy/MBq) while the bone marrow, which is generally the dose-limiting organ for CLR1404, appears to have the lowest (0.063?±?0.005 Gy/MBq). At administered activities of up to 74?MBq (3.7 GBq/kg), mice did not experience signs of toxicity. In addition, a single dose of CLR 125 reduced the volume of orthotopic primary TNBC xenografts by ?60% compared to control vehicle (p?<?0.001) and significantly extended survival. In addition, CLR 125 was efficacious against preclinical metastatic TNBC models by inhibiting the progression of micrometastases (p?<?0.01). CONCLUSIONS:Targeted radionuclide therapy with CLR 125 displayed significant antitumor efficacy in vivo, suggesting promise for treatment of TNBC micrometastases.

Dataset Information

Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

Publications

Auger Electrons Constructed Active Sites on Nanocatalysts for Catalytic Internal Radiotherapy.

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