Fluorescent traceable nanoparticles by co-self-assembly of carbon dot-drug conjugate and biodegradable hyperbranched polymer for diagnosis and therapy

Abstract

Abstract Carbon dots (CDs) have attracted more interest in tumor theranostics, but they suffer from the rapid renal clearance due to small size and high hydrophilicity. To solve such problems, hydrophobic pH-triggered carbon dot-drug conjugate (CDs-Hy-DOX) with high doxorubicin (DOX) content of 48.23% were designed by covalent conjugation of DOX onto the CDs via acid-labile linkage with hydrazine (Hy) as bridge. Then the fluorescent traceable hybrid prodrug nanoparticles were fabricated via co-self-assembly with the CDs-Hy-DOX as pH-sensitive prodrug and a pH/reduction dual-triggered degradable hyperbranched polymer PEG-PO-Cy as polyethylene glycol (PEG)-based surfactant, as well as gatekeeper for pH/reduction dual-triggered DOX release. The hybrid prodrug nanoparticles with hydrodynamic diameter of 220 nm and DOX content of 22.99% were obtained with the optimized co-self-assembling condition. They could release 68.98% of DOX in the simulated tumor microenvironment within 3 days in a sustained release mode, with a premature drug leakage of 7.58%. After the acid-triggered DOX release from the CDs-Hy-DOX, which was accelerated by the pH/reduction dual-triggered degradation of the hyperbranched polymer, the strong fluorescence of CDs-Hy was recovered, demonstrating the promising potential in future tumor nanotheranostics.