J o u r n a l P r e -p r o o f 2 Graphical Abstract Highlights Photoactive TiO2 nanomaterials can solve the actual microbial infectious defies The microbial cell/TiO2 surface approach is key to get the photo-kill mechanism Microbial preparation requires a reproducible protocol for proper characterization Advanced surface characterization techniques can unravel the photo-kill mechanism Generation of ROS, physical injuries and biocidal features confirm the annihilation J o u r n a l P r e -p r o o f Abstract The approach of this timely review considers the current literature that is focused on the interface nanostructure/cell-wall microorganism to understand the annihilation mechanism. Morphological studies use optical and electronic microscopes to determine the physical damage on the cell-wall and the possible cell lysis that confirms the viability and microorganism death. The key parameters of the tailoring the surface of the photoactive nanostructures such as the metal functionalization with bacteriostatic properties, hydrophilicity, textural porosity, morphology and the formation of heterojunction systems, can achieve the effective eradication of the microorganisms under natural conditions, ranging from practical to applications in environment, agriculture, and so on. However, to our knowledge, a comprehensive review of the microorganism/nanomaterial interface approach has rarely been conducted. The final remarks point the ideal photocatalytic way for the effective prevention/eradication of microorganisms, considering the resistance that the microorganism could develop without the appropriate regulatory aspects for human and ecosystem safety. Introduction and background 1. TiO 2 based materials obtained from TiO 2 and its composites J o u r n a l P r e -p r o o f previous studies have demonstrated that photocatalysis can be considered a promising tool in anticancer therapies, since the photocatalyst can kill cancer cells such as HeLa cells, which cause cervical cancer [7]. The energy absorbed by the photocatalyst comprises the range of ultraviolet and/or visible light, even natural sunlight. When the photocatalyst absorbs light, if the energy of the photons is enough to excite the electrons J o u r n a l P r e -p r o o f 6in the valence band (VB), then they migrate to a higher energy level in the conduction band (CB) of the material, as it is illustrated in Fig. 1. This phenomenon generates the charge carriers known as hole-electron pairs. The photogenerated hole can migrate to the surface of the material and react with water molecules or hydroxyl ions to produce hydroxyl radicals, while the photoexcited electron in the conduction band can react with the adsorbed molecular oxygen to produce superoxide ions [8]. Since the report of Fujishima and Honda about the water splitting process using a TiO2 electrode under UV irradiation, numerous studies have exploited the photoactive properties of this material [9,10]. Several reviews have studied the relationship between the electronic properties of TiO2 with...