Abstract

Stimuli-responsive drug release and photodynamic therapy (PDT) have aroused extensive attention for their enormous potential in antitumor treatment. pH-responsive drug delivery systems (PFE-DOX-1 and PFE-DOX-2) based on water-soluble conjugated polymers were constructed in this work for high-performance synergistic chemo-/PDT therapy, in which the anticancer drug doxorubicin (DOX) is covalently attached to the side chains of the conjugated polymers via acid-labile imine and acylhydrazone bonds. Concurrently, the intense fluorescence of poly(fluorene-co-ethynylene) (PFE) is effectively quenched due to the energy/electron transfer (ET) between the PFE-conjugated backbone and DOX. Effective pH-responsive drug release from PFE-DOX-2 is achieved by the cleavage of acylhydrazone linkages in the acidic tumor intracellular microenvironment. Additionally, the drug release process can be monitored by the recovered fluorescence of conjugated polymers. Furthermore, the conjugated polymers can produce reactive oxygen species (ROS) under light irradiation after drug release in an acidic environment, which prevents possible phototoxicity to normal tissues. It is noted that PFE-DOX-2 demonstrates remarkable antitumor cell performance, which is attributed to its efficient cell uptake and powerful synergistic chemo-/PDT therapeutic effectiveness. This report thus provides a promising strategy for in vivo anticancer treatment with the construction of a stimuli-responsive multifunctional drug delivery system.Keywords:conjugated polymer;drug release;photodynamic therapy;chemotherapy;antitumor treatment;synergistic therapy