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Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake.

ABSTRACT: Background and purpose:Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. Their amphiphilic character allows the encapsulation of hydrophobic drugs. Importantly, the hydrophilic/hydrophobic balance determines drug loading and biological interactions. In particular, protein adsorption to NG surfaces is dependent on hydrophobicity and critically determines circulation time. Our study investigates how network hydrophobicity influences protein binding, biocompatibility and cellular uptake. Methods:Biocompatibility of the NGs was examined by WST-1 assay in monocytic-like THP-1 cells. Serum protein corona formation was investigated using dynamic light scattering and two-dimensional gel electrophoresis. Proteins were identified by liquid chromatography-tandem mass spectrometry. In addition, cellular uptake was analyzed via flow cytometry. Results:All NGs were highly biocompatible. The protein binding patterns for the two most hydrophobic NGs were very similar to each other but clearly different from the hydrophilic ones. Overall, protein binding was increased with increasing hydrophobicity, resulting in increased cellular uptake. Conclusion:Our study supports the establishment of structure-property relationships and contributes to the accurate balance between maximum loading capacity with low protein binding, optimal biological half-life and good biocompatibility. This is an important step to derive design principles of amphiphilic NGs to be applied as drug delivery vehicles.

SUBMITTER: Bewersdorff T

PROVIDER: S-EPMC6769055 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake.

Bewersdorff Tony T Gruber Alexandra A Eravci Murat M Dumbani Malti M Klinger Daniel D Haase Andrea A

International journal of nanomedicine 20190926

<h4>Background and purpose</h4>Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. ...[more]

PMID: 31576128

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Project description:PurposeProtein adsorption onto nanoparticles in the form of protein corona, affects properties of nanomaterials and their behavior in the biological milieu. This study aims at exploring the effects of multiwalled carbon nanotubes (MWCNTs) surface chemistry on bovine serum albumin (BSA) and immunoglobulin G (IgG), including their adsorption behavior and spatial configurations, as well as the impact on cellular uptake, cytotoxicity, and cellular responses.MethodsThree types of MWCNTs (pristine MWCNTs, MWCNTs-COOH, and MWCNTs-PEG) were synthesized by classical chemical reduction. The size, morphology, hydrodynamic size, and zeta potential were characterized using transmission electron microscopy and dynamic light scattering. MWCNTs were exposed to BSA and IgG solutions, then the amount of MWCNT absorption was performed by bicinchoninic acid assay, and the effects were assessed by utilizing fluorescence spectroscopy, circular dichroism (CD) spectroscopy. Quantitative measurement of MWCNTs uptake with or without protein corona was performed as turbidity method. CCK assay and a microdilution method were performed to evaluate the effects of protein corona on cytotoxicity and pro-inflammatory cytokines release.ResultsThe BSA and IgG adsorption capacities of MWCNTs followed the order pristine MWCNTs>MWCNTs-COOH and MWCNTs-PEG. MWCNT binding can cause fluorescence quenching and conformational changes in BSA and IgG, indicating that both the physicochemical properties of MWCNTs and protein properties play critical roles in determining their adsorption behavior. Further study showed time-dependent increases in MWCNT cellular uptake and internalization. Hydrophobicity is the major factor increasing cellular uptake of pristine MWCNTs, but a protein corona enriched with dysoposnins is the main factor reducing uptake of MWCNT-COOH by RAW264.7 cells. The cytotoxicity and pro-inflammatory response related to physicochemical properties of MWCNTs, and frustrated phagocytosis is a key initiating event in the pro-inflammatory response of MWCNT-exposed macrophages.ConclusionThese findings shed light on how functionalized MWCNTs interact with protein coronas and provide useful insight into the dramatic effect of protein coronas on different functionalized MWCNTs. These events affect cellular uptake and cytotoxicity, which could inform how to enhance MWCNT biocompatibility and develop approaches for managing MWCNT hazards.

Dataset Information

Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake.

Publications

Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake.

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