Abstract
Background: When nanoparticles (NPs) are applied into a biological fluid, such as blood, proteins bind rapidly to their surface forming a so-called “protein corona”. These proteins are strongly attached to the NP surface and confers them a new biological identity that is crucial for the biological response in terms of body biodistribution, cellular uptake, and toxicity. The corona is dynamic in nature and it is well known that the composition varies in dependence of the physicochemical properties of the NPs. In the present study we investigated the protein corona that forms around poly(lactide-co-glycolide) (PLGA) NPs at different serum concentrations using two substantially different serum types, namely fetal bovine serum (FBS) and human serum. The corona was characterized by means of sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), Bradford protein assay, zeta potential measurements, and liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS). Additionally, the time-dependent cell interaction of PLGA NPs in the absence or presence of a preformed protein corona was assessed by in vitro incubation experiments with the human liver cancer cell line HepG2.Results: Our data revealed that the physiological environment critically affects the protein adsorption on PLGA NPs with significant impact on the NP–cell interaction. Under comparable conditions the protein amount forming the protein corona depends on the serum type used and the serum concentration. On PLGA NPs incubated with either FBS or human serum a clear difference in qualitative corona protein composition was identified by SDS-PAGE and LC–MS/MS in combination with bioinformatic protein classification. In the case of human serum a considerable change in corona composition was observed leading to a concentration-dependent desorption of abundant proteins in conjunction with an adsorption of high-affinity proteins with lower abundance. Cell incubation experiments revealed that the respective corona composition showed significant influence on the resulting nanoparticle–cell interaction.Conclusion: Controlling protein corona formation is still a challenging task and our data highlight the need for a rational future experimental design in order to enable a prediction of the corona formation on nanoparticle surfaces and, therefore, the resulting biodistribution in the body.
Highlights
Nanoparticle (NP)-based drug carrier systems offer outstanding opportunities in the treatment of many serious diseases
In the present study we investigated the protein corona that forms around poly(lactide-co-glycolide) (PLGA) NPs at different serum concentrations using two substantially different serum types, namely fetal bovine serum (FBS) and human serum
Controlling protein corona formation is still a challenging task and our data highlight the need for a rational future experimental design in order to enable a prediction of the corona formation on nanoparticle surfaces and, the resulting biodistribution in the body
Summary
Nanoparticle (NP)-based drug carrier systems offer outstanding opportunities in the treatment of many serious diseases. NPs can be administered via different routes, such as intravenous, intradermal, oral administration or via inhalation During their journey through the body, NPs are exposed to changing biological microenvironments containing different protein compositions and concentrations affecting the corona formation with possible deep implications on the physiological response [3,16]. This emphasizes the great importance of examining the effects provoked by these environmental factors in order to successfully introduce and firmly establish new nanoparticulate dosage forms onto the market, offering further options to prevent and treat many major illnesses. The timedependent cell interaction of PLGA NPs in the absence or presence of a preformed protein corona was assessed by in vitro incubation experiments with the human liver cancer cell line HepG2
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