Degradable cationic shell cross-linked knedel-like nanoparticles: synthesis, degradation, nucleic acid binding, and in vitro evaluation. Academic Article uri icon

abstract

  • In this work, degradable cationic shell cross-linked knedel-like (deg-cSCK) nanoparticles were developed as an alternative platform to replace similar nondegradable cSCK nanoparticles that have been utilized for nucleic acids delivery. An amphiphilic diblock copolymer poly(acrylamidoethylamine)(90)-block-poly(DL-lactide)(40) (PAEA(90)-b-PDLLA(40)) was synthesized, self-assembled in aqueous solution, and shell cross-linked using a hydrolyzable cross-linker to afford deg-cSCKs with an average core diameter of 45 7 nm. These nanoparticles were fluorescently labeled for in vitro tracking. The enzymatic- and hydrolytic-degradability, siRNA binding affinity, cell uptake and cytotoxicity of the deg-cSCKs were evaluated. Esterase-catalyzed hydrolysis of the nanoparticles resulted in the degradation of ca. 24% of the PDLLA core into lactic acid within 5 d, as opposed to only ca. 9% degradation from aqueous solutions of the deg-cSCK nanoparticles in the absence of enzyme. Cellular uptake of deg-cSCKs was efficient, while exhibiting low cytotoxicity with LD50 values of ca. 90 and 30 g/mL in RAW 264.7 mouse macrophages and MLE 12 cell lines, respectively, ca. 5- to 6-fold lower than the cytotoxicity observed for nondegradable cSCK analogs. Additionally, deg-cSCKs were able to complex siRNA at an N/P ratio as low as 2, and were efficiently able to facilitate cellular uptake of the complexed nucleic acids.

published proceedings

  • Biomacromolecules

author list (cited authors)

  • Samarajeewa, S., Ibricevic, A., Gunsten, S. P., Shrestha, R., Elsabahy, M., Brody, S. L., & Wooley, K. L.

citation count

  • 30

complete list of authors

  • Samarajeewa, Sandani||Ibricevic, Aida||Gunsten, Sean P||Shrestha, Ritu||Elsabahy, Mahmoud||Brody, Steven L||Wooley, Karen L

publication date

  • March 2013