Epidermal Growth Factor Receptor-Targeted Delivery of a Singlet-Oxygen Sensitizer with Thermal Controlled Release for Efficient Anticancer Therapy

Photodynamic therapy (PDT) utilizing light-induced singlet oxygen has achieved attractive results in anticancer fields; however, its development is hindered by limited light penetration depth, skin phototoxicity, tumor hypoxia and PDT-induced hypoxia. Inspired by our previous research work and the limitations of PDT, we introduce a small-molecule targeted drug erlotinib into the singlet oxygen chemical source endoperoxide to achieve an EGFR-targeted PDT-mimetic sensitizer (Y3-1) for anticancer therapy. We demonstrated that the erlotinib-based precise delivery of the singlet oxygen chemical source (in vitro photosensitization) to EFGR-overexpressing tumor cells and tissues. Moreover, the anticancer assays validated that the enhanced anticancer efficacy (in vitro and in vivo) of Y3-1 was due to reversible singlet oxygen thermal release. This study is expected to provide a smart strategy to break through the current roadblock in targeted PDT and achieve a more efficient anticancer therapy model.