Staphylococcus aureus-mimetic control of antibody orientation on nanoparticles

• Published in: Nanomedicine 2019-02, Vol.16, p.267-277
• Main Authors: Shim, Gayong, Kim, Dongyoon, Lee, Sangbin, Chang, Rae Sung, Byun, Junho, Oh, Yu-Kyoung
• Format: Article
• Language: English
• Subjects: Bacteriomimetic nanoparticle; Controlled antibody orientation; Fc-directed binding; Noncovalent modification; Staphylococcus aureus
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.09.007

We designed a bacterio-mimetic nanoparticle that can noncovalently control the orientation of attached antibodies. Liposomes with Fc-binding peptide (FcBP), formulated using FcBP-conjugated PEGylated lipid, were used as model nanoparticles. Compared with control nanoparticles surface-modified with antibody covalently attached via maleimide functional groups (Mal-NPs), FcBP-capped nanoparticles (FcBP-NPs) exhibited greater binding affinity to the target protein. Human epidermal growth factor receptor 2 (HER2)-specific antibody-modified FcBP-NPs (HER2/FcBP-NPs) showed 5.3-fold higher binding affinity to HER2 than isotype IgG antibody-modified NPs, and 2.6-fold higher affinity compared with anti-HER2 antibody-conjugated Mal-NPs. Cellular uptake of HER2/FcBP-NPs in HER2-positive cells was significantly higher than that of other formulations. The biodistribution of HER2/FcBP-NPs was higher than that of antibody-conjugated NPs in HER2-positive tumor tissues, but not in HER2-negative tumors. Our findings suggest the potential of bacteriomimetic nanoparticles for controlling the orientation of antibody attachment. These nanoparticles may have diverse applications in nanomedicine, including drug delivery, molecular imaging, and diagnosis. Staphylococcus aureus escape phagocytosis through surface expression of protein A, which specifically binds to the Fc portion of antibodies. Inspired by S. aureus survival mechanism, we designed a bacterio-mimetic nanoparticle that can noncovalently control the direction of attached antibodies. Here, we demonstrate that tagging nanoparticles with an antibody Fc-binding peptide provides noncovalent, one-step binding of antibodies in a controlled orientation. These nanoparticles may have diverse applications in nanomedicine, including drug delivery, molecular imaging, and diagnosis. [Display omitted]