Peptide-derivatized shell-cross-linked nanoparticles. 1. Synthesis and characterization.
The conjugation of the protein transduction domain (PTD) from the HIV-1 Tat protein to shell-cross-linked (SCK) nanoparticles is reported as a method to facilitate cell surface binding and transduction of SCK nanoparticles. Attaching increasing numbers of peptide sequences to SCK nanoparticles in a global solution-state functionalization strategy has been devised as a method for increasing the efficiency of the cell-penetrating process. The numbers of peptides per SCK were controlled through stoichiometric balance and measured experimentally by two independent methods, UV-visible spectroscopy and phenylglyoxal analysis. PTD was conjugated in (0.005, 0.01, and 0.02) molar ratios, relative to the acrylic acid residues in the shell, to the SCK nanoparticles resulting in SCK populations possessing nominally 52, 104, and 210 (41, 83, and 202 as measured by phenylglyoxal analysis) PTD peptides per particle, respectively. The methodologies for the block copolymer and nanoparticle syntheses, peptide derivatization, and characterization of peptide-functionalized SCK nanoparticles are reported and the feasibility and efficiency of intracellular internalization of the respective SCKs were quantified.
Becker, ML; Remsen, EE; Pan, D; Wooley, KL
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