Fabrication of human serum albumin–imprinted photothermal nanoparticles for enhanced immunotherapy

Abstract

Photothermal nanoparticles have been confirmed to induce an antitumor immune response and turn “cold tumor” into “hot tumor”. However, their delivery efficacy to tumors is limited by the elimination from the reticalendothel system. Herein, human serum albumin (HSA)-imprinted polymer coated Fe₃O₄ nanoparticles (Fe₃O₄@MIPs) are fabricated by oxidative polymerization of dopamine in the presence of HSA on the polydopamine pre-modified Fe₃O₄ nanoparticle surface, followed by the removal of HSA. The Fe₃O₄@MIPs exhibit rapid and specific reabsorption toward HSA. The molecularly imprinted sites on the Fe₃O₄@MIPs endow it with an albumin-rich protein corona in the blood and result in less elimination from the reticalendothel system than non-albumin-imprinted particles (Fe₃O₄@NIPs). Moreover, the molecularly imprinted polymer, which consists of polydopamine, also improves the photothermal effect of Fe₃O₄ nanoparticles. In vivo, the albumin camouflage in Fe₃O₄@MIPs produces a 2.6-fold improvement in tumor accumulation in comparison to Fe₃O₄@NIPs, and more heat is produced upon 808 nm laser irradiation, which further triggers an efficient immunogenic cell death (ICD) progress. Thus, the combination of Fe₃O₄@MIPs and PD-L1 antibody can not only inhibit the growth of primary tumors but also eliminates lung metastasis by eliciting immunological effect.