Folic acid-tethered poly(N-isopropylacrylamide)-phospholipid hybrid nanocarriers for targeted drug delivery

A series of temperature-responsive lipopolymers have been synthesized by bioconjugating poly(N-isopropylacrylamide)_n (n = 25, 40, 60) onto three different phospholipids by the combination of reversible addition fragmentation chain transfer polymerization and azide-alkyne click reactions. To achieve the active targeting of cancer cells, folic acid (FA) has also been tethered to the resulting hybrid materials. The doxorubicin (Dox) encapsulated uniform nanocarriers (150 nm in diameter) fabricated by the self-assembly of the lipopolymers display temperature responsive controlled release. The FA receptor-mediated delivery of Dox was then assessed using KB cell lines, and the anti-cancer activity was assessed by the blocking of folic acid receptors. The FA-tethered lipopolymers showing temperature-responsiveness are advantageous for the cell-specific release of Dox, potentiating their anti-cancer activity.