Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided Photodynamic–Chemo Combination Therapy

• Published in: ACS applied materials & interfaces 2021-07, Vol.13 (29), p.33905-33914
• Main Authors: Yang, De-Chao, Wang, Shuai, Weng, Xiao-Lu, Zhang, Hong-Xia, Liu, Jian-Yong, Lin, Zhonghui
• Format: Article
• Language: English
• Subjects: Biological and Medical Applications of Materials and Interfaces
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c09044

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-NPBDP/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-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/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.