Chiral Artificial Antigen-Presenting Cells Enhancing Tumor Immunotherapy: Evasion of Macrophage Uptake through Inhibition of Serum Protein Corona Formation

Biomimetic artificial antigen-presenting cells (aAPCs)
have emerged
as a promising platform for the immune system activation and modulation.
However, abundant serum proteins in the living body prefer to adsorb
on the aAPC surface to form a protein corona, leading to rapid clearance
of aAPCs by mononuclear phagocytes, causing inefficient tumor immunotherapy
by aAPCs. To achieve long-lasting antitumor immunity, chiral aAPCs
with left-handed (aAPCs-L) or right-handed (aAPCs-D) helices are constructed
via coassembly, chiral induction, chiral memory, and a click reaction.
aAPCs-L can efficiently prevent the formation of a protein corona
since the left-handed helix of aAPCs-L and the right-handed helix
of serum proteins are structurally mismatched. Compared with aAPCs-D
and achiral aAPCs (aAPCs-R), aAPCs-L can extend the blood circulation
half-life from 4.15–4.72 h to more than 24 h via evading macrophage
uptake and clearance, performing sustained activation of antitumor
immune response. In vivo treatment with aAPCs-L results in invisible
residual melanoma on day 25 (but 947.3 ± 122.8 mm2 residual melanoma for aAPCs-R and 656.1 ± 135.0 mm2 residual melanoma for aAPCs-D). This study demonstrates that incorporating
the chiral structure into the design of aAPCs improves pharmacokinetics
and enhances the efficacy of tumor immunotherapy, which provides useful
insights into the development of advanced biomedical materials for
cancer treatment.