Albumin as a Trojan Horse for Polymeric Nanoconjugates Transendothelial Transport across Tumor Vasculatures for Improved Cancer Targeting

摘要

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, its clinical utility has been hindered by lack of efficient delivery of therapeutics into targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through 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. Administration of Alb-NCs in 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 its conventional counterpart PEGylated NCs (PEG-NCs). Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.