A facile self-assembly method is described to prepare PEGylated silica nanocarriers using hydrophobic mesoporous silica nanoparticles and a pluronic F127 polymer. Pluronic capped nanocarriers revealed excellent dispersibility in biological media with cyto-and blood compatibilities.The high surface area and pore volume, good chemical stability and ease of surface functionalization of mesoporous silica nanoparticles (MSNs) make them promising materials for biological applications as drug carriers and theranostic agents.1,2 In addition silica based materials are generally accepted as biocompatible materials by the U.S. Food and Drug Administration (FDA). However, recent studies demonstrated their potential in vitro and in vivo toxicity, especially when their size is reduced to the nano scale. 3,4 Although the toxicity of silica based nanomaterials depends on several factors including particle size, shape, surface chemistry and porosity, [5][6][7] there is a general consensus that chemical structure of the surface is the predominant factor which determines the interactions with biological systems. 8 The surface of bare silica is covered with negatively charged silanol groups, which can electrostatically interact with positively charged tetraalkylammonium moieties of the cell membrane and can lead to cytotoxicity by membranolysis or inhibition of cellular respiration. 8,9 Also, rapid aggregation of silica based nanoparticles in biological media can result in mechanical obstruction in the capillary vessels of several vital organs, leading to organ failure and even death. 10,11 Therefore, replacing the surface silanol groups with biocompatible molecules is essential to improve the biocompatibility of MSNs. Among numerous polymeric or organosilane surface modification ligands, polyethylene glycol (PEG) is the mostly used one due to its well established biocompatibility, hydrophilicity, and antifouling properties.12 However, the PEGylation process has some limitations;(i) it mostly requires tedious organic synthesis and surface modification 13 and (ii) pores of MSNs may be closed by the long PEG polymer chains, which can hinder the drug loading process. To overcome these limitations, here we report a facile self-assembly method using octyl modified hydrophobic MSNs and an amphiphilic block copolymer (F127). F127, a FDA approved biocompatible pluronic polymer, contains two hydrophilic PEG blocks and a hydrophobic polypropylene oxide (PPO) between the two PEG blocks. 14 When the powder of hydrophobic MSNs is added into the F127 solution they are easily transferred into water by selfassembly of F127 molecules onto the MSN surface through the hydrophobic interaction between the PPO block of F127 and surface octyl groups of the MSNs (Scheme 1). In addition, cargo loaded and PEGylated MSNs can be simply prepared by loading the hydrophobic MSNs before the F127 capping process. The F127 capped particles are dispersible in both water and phosphate buffered saline (PBS), whereas uncapped MSNs are easily aggregated and precipitated...