热敏脂质体DOX响应释放.pdfVIP

Biomacromolecules 2010, 11, 1915–1920 1915 Thermosensitive Liposomes Modified with Poly(N-isopropylacrylamide-co-propylacrylic acid) Copolymers for Triggered Release of Doxorubicin Terence Ta,* Anthony J. Convertine, Christopher R. Reyes, Patrick S. Stayton, and Tyrone M. Porter Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, Department of Bioengineering, University of Washington, Seattle, Washington 98195 Received May 6, 2010; Revised Manuscript Received June 25, 2010 A novel polymer-modified thermosensitive liposome (pTSL) was developed for the delivery of Doxorubicin (DOX) for cancer therapy. Copolymers containing temperature-responsive N-isopropylacrylamide (NIPAAm) and pH- responsive propylacrylic acid (PAA) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, yielding copolymers with dual pH/temperature-dependent phase transition properties. When attached to liposomes, these copolymers were membrane-disruptive in a pH/temperature-dependent manner. pTSL demonstrated enhanced release profile and significantly lower thermal dose threshold when compared to traditional thermosensitive formulations and were stable in serum with minimal drug leakage over time. These liposomes thus have the potential to dramatically reduce the risk of damage to healthy tissues that is normally associated with liposomal cancer therapy. Introduction containing thermosensitive l