Temperature‐Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma

Abstract

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.

Protein Corona Composition of Gold Nanocatalysts

“…Third, the corona did not show a significant increase in complement proteins and fibrinogens compared to plasma. This suggests a reduced potential of NP eradication by the immune system, which in part, is due to the significant contribution of apolipoproteins to their corona profiles. − More specifically, there were minor variations observed in the concentrations of different types of fibrinogens (such as an increase in the fibrinogen alpha chain) at the initial stages of incubation (Figure ). However, these changes normalized to plasma levels over time, indicating a dynamic equilibrium of fibrinogen adsorption and desorption on the NPs’ surface.…”

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

“…271 (D) Confocal microscopy images of cells incubated in DMEM + 10% FBS and 20% O 2 at 37 1C for different time points under each condition, which showed increased internalization rates in cells treated with MIL-100(Fe). 271 This journal is © The Royal Society of Chemistry 2023 systems have been developed, which modulate the loading and release of drugs in carriers by endogenous environmental response-based factors (e.g., pH 288 ) or exogenous stimulus response-based factors (e.g., light, 289 magnetic field, 191 temperature 290 ). The differences between the internal or external environments of cells provide a theoretical basis for designing of environment-responsive nanoparticle systems.…”

“…, pH 288 ) or exogenous stimulus response-based factors ( e.g. , light, 289 magnetic field, 191 temperature 290 ). The differences between the internal or external environments of cells provide a theoretical basis for designing of environment-responsive nanoparticle systems.…”

Engineering Temperature-Responsive Polymer Nanoparticles that Load and Release Paclitaxel, a Low-Molecular-Weight Anticancer Drug

“…This hydrophilicity/hydrophobicity change alters the affinity of NPs to their target. , The affinity change around the LCST has been exploited in protein purification and switchable on/off catalytic reagents . The temperature-responsive characteristics of pNIPAm have attracted special attention in drug discovery because the LCST of pNIPAm can be rigorously controlled by optimizing the structure and composition of the functional monomer …”