Bimodal Tumor-Targeting from Microenvironment Responsive Hyaluronan Layer-by-Layer (LbL) Nanoparticles

• DOI: 10.1021/nn502861t
• Publication Date: 2014-08-06T18:38:36Z
• Authors: Erik C. Dreaden; Stephen W. Morton; Kevin E. Shopsowitz; Jae-Hyeok Choi; Zhou J. Deng; Nam-Joon Cho; Paula T. Hammond
• Keywords: Targeted drug delivery; Nanocarriers

Active targeting of nanoscale drug carriers can improve tumor-specific delivery; however, cellular heterogeneity both within and among tumor sites is a fundamental barrier to their success. Here, we describe microenvironment-responsive layer-by-layer (LbL) polymer carrier that actively targets tumors based on two independent mechanisms: pH-dependent uptake at hypoxic pH hyaluronan-directed cell-surface CD44 receptor, well-characterized biomarker for breast ovarian cancer stem cells. Hypoxic pH-induced structural reorganization hyaluronan-LbL nanoparticles was direct result the nature LbL electrostatic complex, led targeted delivery in vitro vivo, with effective penetration uptake. The selectively bound diminished cell migration vitro, while co-localizing receptor vivo. Multimodal powerful strategy diagnostics therapy be accomplished using single bilayer polyamine hyaluronan that, when assembled, produce dynamic responsive cell–particle interface.