Endoplasmic reticulum targeted AIE bioprobe as a highly efficient inducer of immunogenic cell death

Abstract

Focused oxidative stress of the specific organelles (e.g., endoplasmic reticulum (ER) and mitochondrion) of cancer cells can boost the immunogenic cell death (ICD) effect for cancer immunotherapy. Herein, an ER-targeted bioprobe with aggregation-induced emission (AIE) characteristics (TPE-PR-FFKDEL) was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide, which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke ICD. Compared with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer, TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed cal-reticulin, ATP secretion, and high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP 70) expression. Furthermore, a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.