Bio21 - Research Publications
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ItemCell-Conditioned Protein Coronas on Engineered Particles Influence Immune Responses(AMER CHEMICAL SOC, 2017-02)A protein corona, which forms on engineered particles as soon as they are introduced into biological environments, is known to provide particles with a "biological identity". Protein coronas derived from various biological environments have been demonstrated to alter the cell internalization mechanism, to diminish targeting ability and to induce nanoparticle aggregation. So far, most of these studies have challenged engineered particles with a static biological environment. However, the extracellular environment is highly dynamic due to the process termed "cell-conditioning", in which cells deplete and secrete biomolecules. In this work, we demonstrate that protein coronas formed on engineered particles from such cell-conditioned media affect the biophysical particle properties and protein adsorption differently to protein coronas derived from an unconditioned environment. When investigating particles with protein coronas formed in various biologically relevant environments for their interaction with immune cells, we observed differences in pro-inflammatory cytokine secretion and immune cell apoptosis. We found that the particles either increased or mitigated the secretion of a specific cytokine, depending on the environment where the protein corona was formed. Our study suggests that the use of protein coronas could be useful to engineer drug carriers for elongated circulation, enhanced biocompatibility, and lower toxicity by triggering a specific immune response.
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ItemMonoclonal Antibody-Functionalized Multilayered Particles: Targeting Cancer Cells in the Presence of Protein Coronas(AMER CHEMICAL SOC, 2015-03)Engineered particles adsorb biomolecules (e.g., proteins) when introduced in a biological medium to form a layer called a "corona". Coronas, in particular the protein corona, play an important role in determining the surface properties of particles and their targeting abilities. This study examines the influence of protein coronas on the targeting ability of layer-by-layer (LbL)-assembled polymer capsules and core-shell particles functionalized with monoclonal antibodies. Upon exposure of humanized A33 monoclonal antibody (huA33 mAb)-functionalized poly(methacrylic acid) (PMA) capsules or huA33 mAb-PMA particles to human serum, a total of 83 or 65 proteins were identified in the protein coronas, respectively. Human serum of varying concentrations altered the composition of the protein corona. The antibody-driven specific cell membrane binding was qualitatively and quantitatively assessed by flow cytometry and fluorescence microscopy in both the absence and presence of a protein corona. The findings show that although different protein coronas formed in human serum (at different concentrations), the targeting ability of both the huA33 mAb-functionalized PMA capsules and particles toward human colon cancer cells was retained, demonstrating no significant difference compared with capsules and particles in the absence of protein coronas: ∼70% and ∼90% A33-expressing cells were targeted by the huA33 mAb-PMA capsules and particles, respectively, in a mixed cell population. This result demonstrates that the formation of protein coronas did not significantly influence the targeting ability of antibody-functionalized LbL-polymer carriers, indicating that the surface functionality of engineered particles in the presence of protein coronas can be preserved.