在癌症治疗中引发免疫原性细胞死亡（ICD）是一个重要的挑战，这可能能显著提高患者的生存率。本研究的目的是开发一种治疗诊断一体化纳米载体，能够在静脉注射后介导光热疗法（PTT）时传递细胞毒性热量剂量，并且随后诱导ICD，提高生存率。该纳米载体由红细胞膜（RBCm）嵌入近红外染料IR-780（IR）和伪装锰铁磁性纳米颗粒（RBCm-IR-Mn）构成。RBCm-IR-Mn纳米载体通过大小、形态、表面电荷、磁性、光物理和光热性质进行表征。其光热转换效率发现受大小和浓度影响。细胞死亡机制为PTT后出现晚期凋亡。对于温度在55℃（消融区间）而非44℃（高温）的体外PTT，钙卫蛋白和HMGB1蛋白水平增加，表明消融下诱导ICD。RBCm-IR-Mn随后被静脉注射到携带肉瘤S180的瑞士小鼠体内，5天后进行体内消融PTT。肿瘤体积在随后的120天内进行监测。RBCm-IR-Mn介导的PTT促进了11/12动物的肿瘤退缩，总生存率为85％（11/13）。我们的结果表明，RBCm-IR-Mn纳米载体是PTT诱导肿瘤免疫治疗的理想候选。

Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD elicitation under ablation. RBCm-IR-Mn were then intravenously administered in sarcoma S180-bearing Swiss mice, and in vivo ablative PTT was performed five days later. Tumor volumes were monitored for the subsequent 120 days. RBCm-IR-Mn-mediated PTT promoted tumor regression in 11/12 animals, with an overall survival rate of 85% (11/13). Our results demonstrate that the RBCm-IR-Mn nanocarriers are great candidates for PTT-induced cancer immunotherapy.