Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided...

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (¹O₂)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an ¹O₂-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NP_BDP/PTX nanodrug could generate bright fluorescent signals and high levels of ¹O₂, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NP_BDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NP_BDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.