Enhanced Anti-PDL1 + Cancer Activity of DM1-Loaded-PLA-TPGS Nanoparticles Mediated with MPDL3280A

Combined with immuno-chemotherapy, a new targeting nano-delivery system was constructed to overcome the side effects of emtansine (DM1). DM1 was first encapsulated into star-shaped PLA-TPGS nanoparticles, and then PDL1-monoclonal antibody (MPDL3280A) was covalently conjugated to DM1-PLA-TPGS nanoparticles (DM1-NPs-MPDL3280A). As a new molecular biomaterial for drug delivery, DM1-NPs-MPDL3280A was evaluated by the anticancer activity against MDA-MB-453 (PDL1(high)) cells in vivo/vitro. Experiments demonstrated that DM1-NPs-MPDL3280A can specifically target PDL1(+) cancer cells. Most strikingly, compared with conventional DM1 and DM1-loaded-PLA-TPGS copolymer NPs (DM1-NPs), DM1-NPs-MPDL3280A showed significantly enhanced cytotoxicity and increased cell apoptosis in PDL1(+) cancer cells. It might be a potential formulation for targeting immuno-chemotherapy to PDL1(+) tumor.