Programmed Nanococktail Based on pH-Responsive Function Switch for Self-Synergistic Tumor-Targeting Therapy

Tumor-targeting combination chemotherapy is an important way to improve the therapeutic index and reduce the side effects as compared to traditional cancer treatments. However, one of the major challenges in surface functionalization of nanoparticle (NP) is accomplishing multiple purposes through one single ligand. Upon such consideration, methotrexate (MTX), an anticancer drug with a targeting moiety inspired by the similar structure of folate, could be used to covalently link with lipid-polymer conjugate (DSPE-PEG) via a pH-sensitive dynamic covalent imine (CH═N) bond to synthesize the acid-induced function “targeting-anticancer” switching DSPE-PEG-CH═N-MTX. We hypothesize that using this kind of MTX prodrug to functionalize NP’s surface would be conductive to combine the early phase active targeting function and the late-phase anticancer function in one nanosystem. Herein, a nanococktail is programmed for codelivery of epirubicin (EPI) and MTX by co-self-assembly of acid-dissociated EPI-phospholipid (P...