研究动态
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负载SN-38的巨噬细胞膜包被的普鲁士蓝纳米粒子的仿生修饰通过光热化疗治疗结直肠癌。

Biomimetic modification of macrophage membrane-coated prussian blue nanoparticles loaded with SN-38 to treat colorectal cancer by photothermal-chemotherapy.

发表日期:2024 Sep 09
作者: Xuyang Hou, Zuxing Wei, Xiaoyan Qi, Dekun Liu, Yin Sun, Yuhong Jiang, Chao Liu, Weihan Zhou, Leping Yang, Kuijie Liu
来源: Drug Delivery and Translational Research

摘要:

SN-38 是伊立替康的活性代谢物,是一种有效的拓扑异构酶 I 抑制剂,对许多恶性肿瘤(包括一些耐药癌症)具有治疗作用。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提供了一种有效的仿生方法来开发新型 SN-38 制剂以减少其副作用。光热疗法(PTT)是一种很有前途的肿瘤治疗方法,利用普鲁士蓝纳米颗粒(NP)等各种材料热消融肿瘤,并且可以与化疗相结合发挥协同作用。目前尚无SN38联合光热疗法治疗结直肠癌(CRC)的报道。 SN38-PB@CM NPs 是通过将 SN-38 负载到巨噬细胞膜包被的中空介孔普鲁士蓝 (PB) NPs 中而构建的。通过透射显微镜和动态光散射(DLS)评估形态、尺寸和zeta电位。进行考马斯亮蓝染色以评估总蛋白质谱。还通过近红外成像研究了它的光热特性。 CCK8和钙黄绿素-AM/PI染色用于评估细胞活力。进行流式细胞术来评估细胞凋亡。使用荧光显微镜观察细胞对 SN38-PB@CM NP 的摄取,以评估其体外内化情况。通过体内成像系统在 CT26 荷瘤小鼠中评估 SN38-PB@CM NP 的体内生物分布、肿瘤靶向功效、抗肿瘤功效和安全性。成功构建了SN38-PB@CM NPs,并表现出均匀的粒径分布(140.5±4.3 nm)和优异的载药量(5.61±0.64%)。 SN38-PB@CM NP 在 72 小时内表现出稳定的释放特性。它还可以在体外增强 SN38 的选择性细胞内递送,并表现出良好的近红外 (NIR) 光热特性。 NPs对携带CT26的小鼠表现出优异的肿瘤靶向性、有效的光热治疗、改善的生物安全性和抗肿瘤功效。多功能SN38-PB@CM NPs可以实现更高的生物安全性、良好的肿瘤靶向性、高效的PTT和优异的抗肿瘤功效,为CRC的治疗提供了一种有前途且有吸引力的联合疗法。© 2024。控释协会。
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.© 2024. Controlled Release Society.