Hyaluronic acid/poly(β-amino ester) polymer nanogels for cancer-cell-specific NIR fluorescence switch

Cancer-cell-specific pH-activatable polymer nanogels consisting of CD44-receptor-targeting hyaluronic acid (HA), pH-sensitive poly(β-amino ester) (PBAE), and near-infrared (NIR) fluorescent indocyanine green (ICG) were synthesized and used to detect cancer cells. The HA/PBAE/ICG-polymer-nanogel-based NIR probe was nonfluorescent outside of tumor cells. After internalization by CD44-receptor-mediated endocytosis, the probe accumulated in the late endosomes or lysosomes where the acidic pH solubilized the PBAE and caused instant disassembly of the polymer nanogel. During endosomal maturation, the encapsulated ICG was released from its quenched state, inducing strong NIR fluorescence recovery. The nanogels generate a highly tumor-specific NIR signal with a reduced background signal.