“Balloon-like” biomimetic erythrocyte vesicles potentiate photodynamic therapy for inducing immunogenic cell death

Abstract

Photodynamic therapy (PDT) for cancer is known for its minimal invasiveness and safe characteristics, but the hypoxic tumor microenvironment still limits efficacy. Herein, we have developed a novel “balloon-like” biomimetic erythrocyte vesicle, which is constructed by loading chlorin e6 (Ce6) and oxygenated hemoglobin (Hb) in a folate (FA)-modified, PEGylated liposome, denoted as Ce6-Hb-FA@lip (CHFL). The CHFL exhibits high biocompatibility and good stability in PBS solution. Moreover, CHFL possesses the “balloon-like” elastic structure for oxygen binding with the change of volume. Both in vitro and in vivo studies demonstrate an effective PDT of CHFL, which significantly reverses the hypoxic microenvironment of tumor cells through the targeted cotransmission of Ce6 and Hb. Additionally, this biomimetic erythrocyte vesicle can induce oxidative stress to enhance tumor immunogenicity and trigger immunogenic cell death (ICD). Thus, the dying tumor cells can activate both dendritic cells (DCs) and T lymphocytes, which, in turn, initiates the antitumor immune response by releasing the damage-associated molecular patterns (DAMPs). This effective and safe platform holds great promise in the development of nanomedicines for innovative oxygen-enhanced PDT in the treatment of cancer.