title: Lung cancer cellular apoptosis induced by recombinant human endostatin gold nanoshell-mediated near-infrared thermal therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China ; Oncology Center, The Affiliated Hospital of Guangdong Medical College Zhanjiang, 524001, China.
authors: Haiqing
authors: H
authors: Luo
authors: Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China.
authors: Meng
authors: M
authors: Xu
authors: Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China.
authors: Xinhai
authors: X
authors: Zhu
authors: Department of Oncology, The First Affiliated Hospital, Jinan University Guangzhou, 510630, China.
authors: Jianfu
authors: J
authors: Zhao
authors: Department of Electronic Engineering, Institute of Nano-Chemistry, Jinan University Guangzhou 510632, China.
authors: Shiqing
authors: S
authors: Man
authors: Department of Electronic Engineering, Institute of Nano-Chemistry, Jinan University Guangzhou 510632, China.
authors: Haoran
authors: H
authors: Zhang
keywords: Gold nanoshells; lung cancer; recombinant human endostatin