Target-Amplified Drug Delivery of Polymer Micelles Bearing Staudinger Ligation

Bioorthogonal chemistry together with biomarker-installing techniques is very promising in the amplification of the tumor targeting efficiency of nanomedicine. In this work, we newly synthesized an amphiphilic block copolymer polyoxazoline-block-polycaprolactone (POX-PCL) in which a certain number of amino groups were dangled in the side chain of the POX block and then functionalized into triarylphosphine groups for active tumor targeting via Staudinger ligation. By using the block copolymer self-assembly, the Staudinger ligation reagent-containing and drug-loaded reactive micelles were prepared with a hydrodynamic diameter of ∼74 nm. Such drug-loaded reactive POX-PCL micelles exhibited significant tumor target ability through the Staudinger ligation between the micelles and the tumors metabolically labeled with azide group, as demonstrated by a series of in vitro and in vivo evaluations. In this work, a novel method was proposed for the application of Staudinger ligation in the nanomedicine for amplifying the tumor targeting ability and antitumor activity of nanodrugs.