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Induction of cytotoxicity by photoexcitation of TiO 2 can prolongsurvival in glioma-bearing miceChao Wang • Shouqiang Cao • Xinxin Tie • Bo Qiu •Anhua Wu • Zhihong ZhengReceived: 19 November 2009/Accepted: 23 March 2010/Published online: 30 March 2010? Springer Science+Business Media B.V. 2010Abstract We have investigated the possibility thatphotoexcited titanium dioxide (TiO 2 ) could inhibit thegrowth of malignant cells. We studied the anti-gliomaeffects of nano-TiO 2 excited with ultraviolet A (UVA)irradiation both in vitro and in vivo. Transmission electronmicroscopy demonstrated that glioma cells take up TiO 2 byphagocytosis, and vital staining revealed that TiO 2 alonehas no effect on glioma cell proliferation. However, if TiO 2was combined with UVA irradiation the proliferationrate was decreased significantly compared to controls(P\0.05). RT–PCR suggested that TiO 2 induction ofglioma cell apoptosis is associated with changes in theexpression of genes encoding Bcl-2 family members. Wethen investigated the in vivo antitumor effects of combinedTiO 2 plus UVA treatment of established glioma tumors.TiO 2 plus UVA led to pronounced areas of necrosis, ele-vated indices of apoptosis, delayed tumor growth, andincreased survival compared with the TiO 2 -alone controlgroup (P\0.001). Log-rank survival analysis showedthat median survival duration was prolonged (P\0.001).These findings suggest that nano-TiO 2 based photodynamictherapy has potential in the treatment of glioma.Keywords Titanium dioxide ? Photodynamic therapy ?Glioblastoma multiforme ? Apoptosis ? Survival ?Nude miceIntroductionGlioblastoma multiforme (GBM), a lethal brain tumor, is aleading cause of death due to solid tumors in people under20, and accounts for 25% of all primary brain tumors inadults [1]. Despite aggressive surgical resection and con-current radiochemotherapy, the prognosis for GBMpatients remains poor with 2-year survival below 27% [2].In consequence there is an urgent need for adjuvant ther-apies for patients with GBM. New therapeutic strategiesthat have been evaluated include treatment with a dipep-tidyl boronic acid inhibitor of the 26S proteasome [3] and achemosensitizer [4], and encouraging results have beenobtained. Because radical surgery is the primary thera-peutic strategy for glioma such tumors are good candidatesfor photodynamic therapy (PDT) [5]. However, intrave-nous administration of photosensitizer (PS) can haveprolonged systemic adverse effects [6] and the PS con-centrations achieved in the target tumor are often insuffi-cient for effective tumor eradication. Moreover, metastaticglioma growth at second sites is typically encounteredfollowing surgery, and glioma is therefore a strong candi-date for local delivery of PS.The medical use of titanium dioxide (TiO 2 )-based bio-materials has recently attracted considerable attention inview of their biocompatibility [7]. In an in vivo study, TiO 2particles alone were found to be non-toxic to experimentalanimals [8]. In addition, it has been shown that TiO 2 can bephotocatalytically activated to become highly cytotoxic forcancer cells [9]. Following UV excitation, activated TiO 2has potent oxidative activity due to the high energy of thephoto-induced electron–hole pairs. These electrons andholes can lead to the generation of reactive oxygen species(ROS), including O 2- and OH • radicals with strong oxi-dative properties, and these in turn lead to structuralC. Wang ? S. Cao ? X. Tie ? B. Qiu ? A. Wu (&)Department of Neurosurgery, First Hospital of China MedicalUniversity, No. 155, North Nanjing Street, Heping District,Shenyang, Liaoning 110001, People’s Republic of Chinae-mail: cmuwuanhua@gmail.comZ. ZhengLaboratory Animal Center of China Medical University,Shenyang 110001, People’s Republic of China123Mol Biol Rep (2011) 38:523–530DOI 10.1007/s11033-010-0136-9