Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG × CD20)

Abstract

PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation.