仿生修饰的巨噬细胞膜包被的普鲁士蓝纳米粒子载荷SN-38用于光热-化疗联合治疗结直肠癌

SN-38是伊立替康的活性代谢产物，作为一种有效的拓扑异构酶I抑制剂，对多种恶性肿瘤具有治疗作用，包括一些耐药性癌症。然而，SN-38的溶解度差、生物利用度低以及严重的剂量依赖性毒性限制了其临床应用。目前，新兴的巨噬细胞膜包被纳米粒子为开发新型SN-38制剂提供了一种高效的仿生学途径，以减少其副作用。光热疗法（PTT）是一种利用各种材料如普鲁士蓝纳米粒子（NPs）通过热破坏肿瘤的有前景的方法，并可与化疗结合实现协同作用。目前尚无关于SN-38与光热疗法联合用于结直肠癌（CRC）治疗的报道。通过加载SN-38到包覆巨噬细胞膜的空心多孔普鲁士蓝（PB）纳米粒子，构建了SN-38-PB@CM NPs。采用透射电子显微镜和动态光散射（DLS）评估其形态、尺寸和 zeta 电位。通过考马斯亮蓝染色评估总蛋白质谱。利用近红外成像研究其光热性能。采用CCK8和Calcein-AM/PI染色评估细胞活力。流式细胞术检测细胞凋亡。荧光显微镜观察SN38-PB@CM NPs的细胞摄取，以评估其体外内吞作用。在体动物模型中，通过体内成像系统评估SN38-PB@CM NPs在CT26肿瘤携带小鼠中的组织分布、肿瘤靶向效能、抗肿瘤效果及安全性。结果显示，SN38-PB@CM NPs成功构建，具有均匀的粒径分布（140.5 ± 4.3 nm）和优异的药物负载能力（5.61 ± 0.64%）。在72小时内表现出稳定的药物释放特性。能够增强SN-38在细胞内的选择性递送，具有良好的近红外（NIR）光热性能。且其在CT26肿瘤模型中表现出优异的肿瘤靶向性、有效的光热治疗效果、改善的生物安全性和抗肿瘤效果。多功能SN38-PB@CM NPs实现了改善的生物安全性、出色的肿瘤靶向性、高效的PTT和优异的抗肿瘤效果，为CRC的治疗提供了具有前景的联合治疗策略。

SN-38 is the active metabolite of irinotecan and acts as an effective topoisomerase I inhibitor with therapeutic effects on many malignant tumors, including some drug-resistant cancers. However, the poor solubility, low bioavailability, and severe dose-dependent toxicity limits the clinical application of SN-38. Currently, emerging macrophage membrane-coated nanoparticles provide an efficient biomimetic approach to develop novel SN-38 formulations for the reduction of its side effects. Photothermal therapy (PTT) is a promising methods in tumor treatment to thermally ablate tumors using various materials such Prussian blue nanoparticles (NPs) and can combined with chemotherapy to synergistically work. There is no report that combined SN38 and photothermal therapy for the treatment of colorectal cancer (CRC). SN38-PB@CM NPs were constructed by loading SN-38 into macrophage cell membrane-coated hollow mesoporous Prussian blue (PB) NPs. The morphology, size and zeta potential were evaluated by transmission microscopy and dynamic light scatter (DLS). Coomassie bright blue staining was performed to assess total protein profile. The photothermal properties of it were also investigated via near-infrared imaging. CCK8 and calcein-AM/PI staining were used to evaluate cell viability. Flow cytometry was performed to assess cell apoptosis. The fluorescent microscopy was used to observe cellular uptake of SN38-PB@CM NPs to assess its internalization in vitro. The biodistribution, tumor-targeting efficacy, antitumor efficacy and safety of SN38-PB@CM NPs in vivo were assessed in CT26 tumor-bearing mice via In Vivo Imaging System. SN38-PB@CM NPs were successfully constructed and exhibited a uniform size distribution (140.5 ± 4.3 nm) and an excellent drug-loading capacity (5.61 ± 0.64%). SN38-PB@CM NPs showed stable release properties within 72 h. It can also enhance the selective intracellular delivery of SN38 in vitro and showed good near-infrared (NIR) photothermal properties. And the NPs showed excellent tumor targeting, effective photothermal therapy, improved biosafety and antitumor efficacy on CT26-bearing mice. Multifunctional SN38-PB@CM NPs could achieve improved biosafety, great tumor-targeting, high-efficiency PTT and excellent antitumor efficacy, which provided a promising and attractive combination therapy for the treatment of CRC.