Genetically engineered macrophage membrane-coated nanoparticles for enhanced tumor targeting and synergistic cancer therapy

Abstract The poor targeting capability of systemically administered drugs is a major hurdle in designing effective therapies with minimal off-target side effects. Here, as a proof of concept, we propose a genetic engineering strategy to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy-1) in the macrophage membrane, which is then coated onto core-shell Fe 3 O 4 @Au nanoparticles to produce a biomimetic nanoplatform, Magic. The results indicate that Magic exhibits not only high specificity and affinity towards prostate tumor cells in vitro and in vivo, but also effective immunomodulatory capability. Upon further encapsulation with the anti-tumor drug DM1, Magic shows superior synergistic effects in highly targeted chemo-photothermal therapy and potent immunotherapy, eliciting significant therapeutic efficacy against tumor growth, micro-metastasis and concomitant damage without overt toxicity. These findings reveal that Magic may provide a promising platform for enhancing cancer treatment by overcoming undesired drug delivery barriers and the tumor immune microenvironment.