PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively. Their capacity of ICD induction, tumor antigen-capture, and antitumor immune responses were evaluated. Both the intrinsic toxicity of PEI and the ICG-mediated photothermal effect were responsible for inducing ICD. The positively charged PEI segment exhibited the best antigen-capturing ability via electrostatic interactions, promoted bone marrow-derived dendritic cell maturation and CD8⁺ T cell proliferation, and elicited antitumor immune responses in vivo. PDS groups bonded antigens covalently and significantly contributed to the suppression of distant tumor growth. Although the thermosensitive hydrophobic polymer segment did not contribute positively to antigen capture or tumor growth inhibition, NPs containing all of the functional modules prolonged the survival of tumor-bearing mice more than other treatments. This study provides more chemical insights into the design of polymer-based in situ nanovaccines against cancer.