Sousa-Junior Ailton Antonio, Mello-Andrade Francyelli, Rocha João Victor Ribeiro, Hayasaki Tácio Gonçalves, de Curcio Juliana Santana, Silva Lívia do Carmo, de Santana Ricardo Costa, Martins Lima Eliana, Cardoso Cléver Gomes, Silveira-Lacerda Elisângela de Paula, Mendanha Sebastião Antonio, Bakuzis Andris Figueiroa
Institute of Physics, Federal University of Goias, Goiania 74690-900, GO, Brazil.
FarmaTec, School of Pharmacy, Federal University of Goias, Goiania 74690-631, GO, Brazil.
Pharmaceutics. 2023 Mar 14;15(3):943. doi: 10.3390/pharmaceutics15030943.
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.
在癌症治疗过程中诱导免疫原性细胞死亡（ICD）是一项重大挑战，这可能会显著提高患者的生存率。本研究的目的是开发一种诊疗纳米载体，它在静脉注射后介导光热疗法（PTT）时既能传递细胞毒性热剂量，又能因此诱导ICD，从而提高生存率。该纳米载体由包埋近红外染料IR-780（IR）并伪装锰铁氧体纳米颗粒的红细胞膜（RBCm）组成（RBCm-IR-Mn）。通过尺寸、形态、表面电荷、磁性、光物理和光热性质对RBCm-IR-Mn纳米载体进行了表征。发现它们的光热转换效率与尺寸和浓度有关。观察到晚期凋亡是PTT的细胞死亡机制。在温度约55℃（消融状态）的体外PTT中，钙网蛋白和HMGB1蛋白水平升高，但在44℃（热疗）时未升高，这表明在消融状态下可引发ICD。然后将RBCm-IR-Mn静脉注射到荷肉瘤S180的瑞士小鼠体内，并在五天后进行体内消融PTT。在随后的120天内监测肿瘤体积。RBCm-IR-Mn介导的PTT促进了12只动物中11只的肿瘤消退，总生存率为85%（11/13）。我们的结果表明，RBCm-IR-Mn纳米载体是PTT诱导癌症免疫治疗的理想候选者。
