A pH-Responsive Drug Delivery System Based on Conjugated Polymer for Effective Synergistic Chemo-/Photodynamic Therapy

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.

A comprehensive review on singlet oxygen generation in nanomaterials and conjugated polymers for photodynamic therapy in the treatment of cancer

“…Yet, unreliable drug leakage could endanger healthy tissues more severely and reduce the effectiveness of the combined anticancer effects. 130 In addition to improving the effectiveness of ROS generation, CPs can play beneficial roles in disease therapy. For example, a large number of side chains are commonly linked to the CP backbones, which may facilitate drug dispersion and responsive drug release.…”

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple‐negative breast cancer

“…The protonation induced by weak acidic pH leads to the hydrophilic to hydrophobic phase transition of nanomaterials (Jia et al, 2021). At the same time, the charge reversal of the anionic polymer induced by protonation gives the nanomaterials a positive charge, promoting enhanced cell absorption and deeper tumor penetration through electrostatic absorption (Chen et al, 2023). Active targeting of pH has also been reported recently.…”

Fluorescent Probes as a Tool in Diagnostic and Drug Delivery Systems

“…Recently, Zhang C. and co-workers constructed a pH-responsive drug delivery system 67 based on a conjugated polymer for effective synergistic chemo-/PDT antitumor therapy ( Figure 63 ) [ 173 ].…”

“… Schematic diagram of pH-responsive drug release and the mechanism of synergistic chemo-/PDT antitumor therapy. Adapted with permission from [ 173 ]. Copyright (2023) MDPI.…”