Conjugated Polymer Nanoparticles Based on Copper Coordination for Real-Time Monitoring of pH-Responsive Drug Delivery

Metal coordination-driven composite systems have excellent stability and pH-responsive ability, making them suitable for specific drug delivery in physiological conditions. In this study, an anionic conjugated polymer PPEIDA with a poly(p-phenylene ethynylene) backbone and iminodiacetic acid (IDA) side chains is used as a drug carrier to construct a class of pH-responsive nanoparticles, PPEIDA-Cu-DOX conjugated polymer nanoparticles (CPNs), by taking advantage of the metal coordination interaction of Cu²⁺ with PPEIDA and the drug doxorubicin (DOX). PPEIDA-Cu-DOX CPNs have high drug loading and encapsulation efficiency (EE), calculated to be 54.30 ± 1.10 and 95.80 ± 0.84%, respectively. Due to the good spectral overlap, Förster resonance energy transfer (FRET) takes place between PPEIDA and the drug DOX, which enables the observation of the loading and the release of DOX from CPNs in an acidic environment by monitoring fluorescence emission changes. Therefore, PPEIDA-Cu-DOX CPNs can also be used in real-time cell imaging to monitor drug release in addition to delivering DOX targeting tumor cells. Compared with free DOX, PPEIDA-Cu-DOX CPNs show a similar inhibition to tumor cells and lower toxicity to normal cells. Our results demonstrate the feasibility and potential of constructing pH-responsive CPNs via metal-ligand coordination interactions for cancer treatment.