Temperature‐responsive polymers display changes of conformation upon a certain threshold temperature, which involves changes of hydrophobicity. Therefore, this property can be exploited to construct materials showing temperature‐dependent interactions with proteins and cells. Indeed, the amounts and types of proteins in the protein corona after incubating temperature‐responsive materials in protein mixtures are regulated by the surface hydrophobicity of materials. This ability is beneficial for designing systems for protein separation or for protecting proteins from thermal stress. Temperature‐responsive materials are also employed for controlling cell adhesion and detachment. The cells are incubated at physiological temperature of mammalians (37 °C) followed by desorption of cell sheets at lower temperature when the substrate is hydrophilic. The authors envision that temperature‐responsive materials will be employed for controlling protein corona of nanocarriers for drug delivery applications.

when injecting nanoparticles into a bloodstream is the clearance of nanoparticles from the blood caused by an unspecific protein adsorption and fast uptake into immune cells like macrophages. [3] Therefore, controlling the protein adsorption around nanoparticles and in consequence controlling the stealth effect is of great importance. [4] Herein, we report a method for preparing a specific protein corona on nanoparticles, which significantly imparts them with a stealth effect.The most straightforward method to provide a stealth effect to nanoparticles is to coat them with apolipoproteins prior to injection. [5] However, isolated apolipoproteins are costly, and therefore, this approach cannot be easily scaled up. Another approach relies on the enrichment of protein corona on the surface of materials with apolipoprotein by incubating functionalized nanoparticles with plasma. [6] The coating of nanocarriers with poly(ethylene glycol) (PEG) or polyphosphoesters was found to favor the adsorption of apolipoproteins. [5,7] The protein adsorption on nanoparticles is known to be temperature-dependent. [8,9] However, no clear correlation between the composition of protein corona and the temperature could be derived. [8] Because the temperature varies in the human body, it is necessary to incubate the nanoparticles ex vivo prior to their use in vivo, in order to prepare a stable and reproducible protein corona.Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-free quantitative liquid chromatography-mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature-dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperatureresponsive materials is a suitable method for imparting stealth properties to nanocarriers for drug-delivery.

Amphiphilic polyphenylene dendrimers adsorbed to liposomes alter the protein corona dependent on their charge and hydrophobicity.