Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogel for cancer detection and treatment

Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) (FA-PEG-NH2) and rhodamine B (RhB)-terminated poly(ethylene glycol) (RhB-PEG-NH2) modified oxidized alginate (OAL-g-PEG-FA/RhB) with cystamine (Cys), followed covalent conjugation of doxorubicin (DOX) via acid-labile Schiff base bond. Owing to the surface folic acid (FA) groups, disulfide crosslinking structure and Schiff base conjugation for DOX, the folate receptor (FR)-mediated targeting and pH/reduction dual responsive intracellular triggered release of DOX was achieved. The cytotoxicity and cellular uptake results clearly illustrated that most DOX was released and accumulated in the cell nuclei and killed the cancer cells efficaciously, due to the desirable targeting intracellular triggered release. Furthermore, the theranostic nanogels could be used for the real-time and noninvasive location tracking to cancer cells, owing to the pH-modulated fluorescence property of the pendant RhB groups.