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Surface chemistry and serum type both determine the nanoparticle-protein corona.

ABSTRACT: The protein corona that forms around nanoparticles in vivo is a critical factor that affects their physiological response. The potential to manipulate nanoparticle characteristics such that either proteins advantageous for delivery are recruited and/or detrimental proteins are avoided offers exciting possibilities for improving drug delivery. In this work, we used nanoliquid chromatography tandem mass spectrometry to characterize the corona of five lipid formulations after incubation in mouse and human plasma with the hope of providing data that may contribute to a better understanding of the role played by both the nanoparticle properties and the physiological environment in recruiting specific proteins to the corona. Notably, we showed that minor changes in the lipid composition might critically affect the protein corona composition demonstrating that the surface chemistry and arrangement of lipid functional groups are key players that regulate the liposome-protein interactions. Notably, we provided evidence that the protein corona that forms around liposomes is strongly affected by the physiological environment, i.e., the serum type. These results are likely to suggest that the translation of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis.In the present work nanoliquid chromatography tandem mass spectrometry was used to characterize the protein corona of five different liposome formulations after exposure to mouse and human plasma. The modern proteomic methods employed have clarified that the arrangement of lipid functional groups is a key player that regulates the liposome-protein interactions. We also clarified that the protein corona enrichment and complexity depend on the serum type. Our results suggest that the translational of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis.

SUBMITTER: Pozzi D

PROVIDER: S-EPMC4441341 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Surface chemistry and serum type both determine the nanoparticle-protein corona.

Pozzi Daniela D Caracciolo Giulio G Capriotti Anna Laura AL Cavaliere Chiara C La Barbera Giorgia G Anchordoquy Thomas J TJ Laganà Aldo A

Journal of proteomics 20150227

The protein corona that forms around nanoparticles in vivo is a critical factor that affects their physiological response. The potential to manipulate nanoparticle characteristics such that either proteins advantageous for delivery are recruited and/or detrimental proteins are avoided offers exciting possibilities for improving drug delivery. In this work, we used nanoliquid chromatography tandem mass spectrometry to characterize the corona of five lipid formulations after incubation in mouse an ...[more]

PMID: 25731725

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Project description: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.

Project description:BackgroundNanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation.ResultsMouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented.ConclusionsThe results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection.

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Surface chemistry and serum type both determine the nanoparticle-protein corona.

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Surface chemistry and serum type both determine the nanoparticle-protein corona.

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