Degradable cationic shell cross-linked knedel-like nanoparticles: Synthesis, degradation, nucleic acid binding, and in vitro evaluation

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

Research output: Contribution to journalArticle

29 Scopus citations

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 (PAEA90-b- PDLLA40) 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 μg/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.

Original languageEnglish
Pages (from-to)1018-1027
Number of pages10
JournalBiomacromolecules
Volume14
Issue number4
DOIs
StatePublished - Apr 8 2013

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