title: Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia.
abstract: Inspired by the simplicity and versatility of layer-by-layer (LbL) assembly, we applied multilayered polyelectrolyte assemblies on nanoparticles to create viable systemic delivery systems. Focusing on tumor-specific delivery, LbL nanoparticles that exhibit a pH-sensitive outer stealth layer are demonstrated to target and be retained in hypoxic tumor regions. The neutral layers shed in response to acidity to reveal a charged nanoparticle surface that is readily taken up by tumor cells. The first in vivo demonstration of this mechanism of targeting is presented, as well as an initial examination of the mechanism of uptake of the nanoparticles. We further demonstrate that this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.
authors.affiliation: The Koch Institute for Integrative Cancer Research at MIT, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Poon
authors.forename: Dongsook
authors.initials: D
authors.lastname: Chang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhao
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004573:Electrolytes; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D004573:Electrolytes; D013778:Tetrazolium Salts; D013844:Thiazoles; D011092:Polyethylene Glycols; C022616:thiazolyl blue