Albumin as a "Trojan Horse" for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting.

Abstract

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.