Osimertinib delivery using 660 nm-activated polymeric nano-photosensitizer carriers for combined photodynamic and EGFR-targeted therapy of non-small cell lung cancer.

Osimertinib (Osi), an EGFR tyrosine kinase inhibitor (TKI), significantly prolongs patients' survival with EGFR-mutated non-small cell lung cancer (NSCLC). However, extended use often leads to acquired resistance, limiting the effectiveness of monotherapy. Photodynamic therapy (PDT) is a minimally invasive modality effective against superficial tumors. Combination PDT with EGFR-targeted therapy may enhance therapeutic efficacy in NSCLC. We developed a photosensitizer-conjugated PLA-based nanocarrier for the co-delivering Osi and hematoporphyrinmonomethyl ether (HMME), integrating EGFR-inhibition and PDT for EGFR-mutated NSCLC. This combination effectively inhibits EGFR kinase activity and the PI3K-AKT-mTOR signaling pathway, while simultaneously activating the PDT effect under 660 nm irradiation, inducing tumor cell apoptosis and preventing spontaneous lung metastasis. Therapeutic efficacy has been validated both in vitro and in vivo using a subcutaneous HCC827 tumor model. These findings suggest that combining 660 nm-activated PDT and EGFR-targeted therapy is a promising treatment strategy for EGFR-mutant NSCLC.