Haiqing Luo1, Meng Xu2, Xinhai Zhu2, Jianfu Zhao2, Shiqing Man3, Haoran Zhang3. 1. Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China ; Oncology Center, The Affiliated Hospital of Guangdong Medical College Zhanjiang, 524001, China. 2. Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China. 3. Department of Electronic Engineering, Institute of Nano-Chemistry, Jinan University Guangzhou 510632, China.
Abstract
AIMS AND BACKGROUND: Endostatin can inhibit tumor endothelial cell proliferation, angiogenesis, and growth. We aimed to determine the increase in antitumor capabilities of recombinant human endostatin (rhES) when used with a nanocarrier system. The effect of gold nanoshell particles of recombinant human endostatin (G-rhES) with near-infrared (NIR) irradiation on proliferation, inhibition, and apoptosis of A549 lung cancer cells was studied. MATERIALS AND METHODS: Gold nanoshell particles were prepared. Endostatin was connected with the bond A-U through surface modification by bioconjugation of core-shell structured gold nanoshells. The drug targeting endostatin and the synthesized G-rhES were successfully connected. G-rhES inhibited proliferation of A549 lung cancer cells, as detected using tetrazolium colorimetric assay. Cellular apoptosis was measured by flow cytometry. Mitochondrial membrane potential was determined using a confocal microscope. Morphological changes were studied by atomic force microscopy. RESULTS: Under irradiation in the 820 nm NIR, G-rhES significantly inhibited the proliferation of A549 lung cancer cells. The underlying mechanism may be related to heat-induced apoptosis and cytotoxicity by NIR absorption, which kills cells directly, thereby indicating that G-rhES have good biocompatibility and pharmacological potency. Characterization of the local structure of lung cancer cells showed that G-rhES targeted surface receptors that may serve an apoptotic function under NIR exposure. NIR gold nanoshell particles showed synergism with endostatin, which may be related to hyperthermia-increased cytotoxicity and the apoptotic effect of endostatin. CONCLUSION: These data suggest that G-rhES can enhance the inhibition of tumor growth. The new treatment strategy of G-rhES combined with thermal therapy may lead to lung cancer remission. The potential benefits of G-rhES are being considered for clinical evaluation.
AIMS AND BACKGROUND:Endostatin can inhibit tumor endothelial cell proliferation, angiogenesis, and growth. We aimed to determine the increase in antitumor capabilities of recombinant humanendostatin (rhES) when used with a nanocarrier system. The effect of gold nanoshell particles of recombinant humanendostatin (G-rhES) with near-infrared (NIR) irradiation on proliferation, inhibition, and apoptosis of A549 lung cancer cells was studied. MATERIALS AND METHODS: Gold nanoshell particles were prepared. Endostatin was connected with the bond A-U through surface modification by bioconjugation of core-shell structured gold nanoshells. The drug targeting endostatin and the synthesized G-rhES were successfully connected. G-rhES inhibited proliferation of A549 lung cancer cells, as detected using tetrazolium colorimetric assay. Cellular apoptosis was measured by flow cytometry. Mitochondrial membrane potential was determined using a confocal microscope. Morphological changes were studied by atomic force microscopy. RESULTS: Under irradiation in the 820 nm NIR, G-rhES significantly inhibited the proliferation of A549 lung cancer cells. The underlying mechanism may be related to heat-induced apoptosis and cytotoxicity by NIR absorption, which kills cells directly, thereby indicating that G-rhES have good biocompatibility and pharmacological potency. Characterization of the local structure of lung cancer cells showed that G-rhES targeted surface receptors that may serve an apoptotic function under NIR exposure. NIR gold nanoshell particles showed synergism with endostatin, which may be related to hyperthermia-increasedcytotoxicity and the apoptotic effect of endostatin. CONCLUSION: These data suggest that G-rhES can enhance the inhibition of tumor growth. The new treatment strategy of G-rhES combined with thermal therapy may lead to lung cancer remission. The potential benefits of G-rhES are being considered for clinical evaluation.
Entities:
Keywords:
Gold nanoshells; lung cancer; recombinant human endostatin
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