| Autor: |
Park JH; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, Singapore.; Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States., Jackman JA; School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.; SKKU-UCLA-NTU Precision Biology Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea., Ferhan AR; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, Singapore., Belling JN; Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States., Mokrzecka N; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, Singapore., Weiss PS; Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States.; SKKU-UCLA-NTU Precision Biology Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea.; Department of Bioengineering and Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States., Cho NJ; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Drive, Singapore 639798, Singapore.; SKKU-UCLA-NTU Precision Biology Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea. |
| Abstrakt: |
Silica-coated nanoparticles are widely used in biomedical applications such as theranostics, imaging, and drug delivery. While silica-coated nanoparticles are biocompatible, experimental evidence shows that they can trigger innate immune reactions, and a broader understanding of what types of reactions are caused and how to mitigate them is needed. Herein, we investigated how the noncovalent surface functionalization of silica nanoparticles with purified proteins can inhibit nanoparticle-induced complement activation and macrophage uptake, two of the most clinically relevant innate immune reactions related to nanomedicines. Silica nanoparticles were tested alone and after coating with bovine serum albumin, human serum albumin, fibrinogen, complement factor H (FH), or immunoglobulin G (IgG) proteins. Enzyme-linked immunosorbent assays measuring the generation of various complement activation products indicated that silica nanoparticles induce complement activation via the alternative pathway. All protein coatings other than IgG protected against complement activation to varying extents. Most proteins acted as steric blockers to inhibit complement protein deposition on the nanoparticle surface, while FH coatings were biologically active and inhibited a key step in the amplification loop of complement activation, as confirmed by Western blot analysis. Flow cytometry and fluorescence microscopy experiments further revealed that complement activation-inhibiting protein coatings blunted macrophage uptake as well. Taken together, our findings demonstrate a simple and effective way to coat silica nanoparticles with purified protein coatings in order to mitigate innate immune reactions. Such methods are readily scalable and might constitute a useful strategy for improving the immunological safety profile of silica and silica-coated nanoparticles as well as other types of inorganic nanoparticles. |
