RESEARCH PAPER Modifications of nano-titania surface for in vitro evaluations of hemolysis, cytotoxicity, and nonspecific protein binding Aparna Datta & Sayantan Dasgupta & Siddhartha Mukherjee Received: 8 December 2016 /Accepted: 24 March 2017 # Springer Science+Business Media Dordrecht 2017 Abstract In the past decade, a variety of drug carriers based on mesoporous silica nanoparticles has been ex- tensively reported. However, their biocompatibility still remains debatable, which motivated us to explore the porous nanostructures of other metal oxides, for exam- ple titanium dioxide (TiO 2 ), as potential drug delivery vehicles. Herein, we report the in vitro hemolysis, cyto- toxicity, and protein binding of TiO 2 nanoparticles, syn- thesized by a sol–gel method. The surface of the TiO 2 nanoparticles was modified with hydroxyl, amine, or thiol containing moieties to examine the influence of surface functional groups on the toxicity and protein binding aspects of the nanoparticles. Our study revealed the superior hemocompatibility of pristine, as well as functionalized TiO 2 nanoparticles, compared to that of mesoporous silica, the present gold standard. Among the functional groups studied, aminosilane moieties on the TiO 2 surface substantially reduced the degree of hemolysis (down to 5%). Further, cytotoxicity studies by MTT assay suggested that surface functional moie- ties play a crucial role in determining the biocompati- bility of the nanoparticles. The presence of NH 2 – func- tional groups on the TiO 2 nanoparticle surface enhanced the cell viability by almost 28% as compared to its native counterpart (at 100 μg/ml), which was in agree- ment with the hemolysis assay. Finally, nonspecific protein adsorption on functionalized TiO 2 surfaces was examined using human serum albumin and it was found that negatively charged surface moieties, like –OH and – SH, could mitigate protein adsorption to a significant extent. Keywords Titanium dioxide . Surface functionalization . Hemolysis . Nonspecific protein binding . Cytotoxicity assay . Biomedical applications Introduction Metal oxide nanoparticles with mesoporous structures have emerged as highly promising vehicles for targeted delivery of therapeutics. Large specific surface area, tunable pore structures, and excellent physico- chemical stability go in favor of such nanovehicles for hosting and site-specific delivery of disparate pay- loads, e.g., molecular drugs, nucleic acids, and pro- teins (Vallet-Regí et al. 2007). Though mesoporous silica nanoparticles (MSN) have been considered as the Bholy grail^ for targeted drug delivery, some re- ports highlight the potential toxicity of MSN, primarily due to the interactions of surface silanol moieties with J Nanopart Res (2017) 19:142 DOI 10.1007/s11051-017-3835-5 A. Datta (*) School of Materials Science and Nanotechnology, Jadavpur University, 188, Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India e-mail: adatta.research@gmail.com S. Dasgupta Department of Biochemistry, NRS Medical College and Hospital, 138 A.J.C. Bose Road, Kolkata, West Bengal 700014, India S. Mukherjee Department of Metallurgical and Material Engineering, Jadavpur University, 188, Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India