Nanomicelle with reversible surface properties as a general adjuvant for potentiating immune responses to multiple types of tumor antigens

Poor antigen presentation efficiency remains the primary challenge of tumor-derived vaccines, mainly due to the inefficient endocytosis of antigens and activation of antigen-presenting cells (APCs). Here, we developed a general ready-to-use adjuvant to enhance the immune response to multiple types of antigens, including tumor cell lysate, tumor cell membrane, antigen protein, and messenger RNA. The adjuvant was synthesised by conjugating cinnamaldehyde onto polyethyleneimine (PC), which self-assembles in the water phase to form nanomicelles. Since the main components of most antigens are proteins or nucleic acids, PC could bind to antigens via hydrophobic or electrostatic interactions and then promote their cellular endocytosis. Notably, in APCs, PC reacted with glutathione (GSH), which not only led to the depletion of GSH and maturation of dendritic cells but also triggered antigen release by reversing the antigen binding force due to GSH's negative charge and hydrophilicity. Thus, the PC adjuvant significantly increased the immunogenicity of tumor cell membranes, tumor cell lysates, and liquid‑nitrogen-shocked tumor cells by 113-, 81-, and 60-fold, respectively, compared to free antigens.