Controlled Fab installation onto polymeric micelle nanoparticles for tuned bioactivity
| Autor: | R. James Christie, Ze Qi Xu, Abigail Teitgen, Changshou Gao, Shaoyi Chen, Herren Wu, Kazunori Kataoka, Horacio Cabral, Stelios Florinas |
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| Rok vydání: | 2017 |
| Předmět: |
Steric effects
Materials science lcsh:Biotechnology Nanoparticle 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Polymeric micelle lcsh:TP248.13-248.65 PEG ratio lcsh:TA401-492 Organic chemistry General Materials Science Cytotoxicity conjugation efficiency chemistry.chemical_classification ligand density Polymeric micelles Polymer Fab modification 021001 nanoscience & nanotechnology 0104 chemical sciences Chemical engineering chemistry bioactivity lcsh:Materials of engineering and construction. Mechanics of materials 0210 nano-technology Macromolecule |
| Zdroj: | Science and Technology of Advanced Materials, Vol 18, Iss 1, Pp 666-680 (2017) |
| DOI: | 10.6084/m9.figshare.5422681.v1 |
| Popis: | Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity. |
| Databáze: | OpenAIRE |
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