负载黑磷量子点的红细胞膜囊泡在乳腺癌光热治疗中的应用

Black phosphrous quantum dot (BPQD)-loaded erythrocyte membrane vesicles for phothothermal therapy in breast cancer

目的建立负载黑磷量子点的红细胞膜纳米囊泡(BPQD-EMNVs)的制备方法,并探讨其在乳腺癌光热治疗中的应用。方法采用液相剥离法制备BPQD,同时提取健康小鼠的新鲜血液制备红细胞膜,再超声制备BPQD-EMNVs。采用透射电子显微镜观察BPQD-EMNVs的形态,纳米粒度及Zeta电位仪测其粒径分布,电感耦合等离子体发射光谱仪测定BPQD的包封率,激光共聚焦显微镜观察小鼠乳腺癌细胞4T1对BPQD-EMNVs的摄取情况。将4T1荷瘤Balb/c小鼠按随机数字表法分为PBS、EMNVs、BPQD和BPQD-EMNVs组,尾静脉注射对应药物4 h后,用808 nm近红外光照射肿瘤部位10 min,观察肿瘤生长情况。结果制备的BPQD-EMNVs呈规则的球形,平均粒径为228 nm,包封率约为47%。细胞摄取实验结果显示,BPQD-EMNVs能迅速被4T1细胞摄取。动物实验结果显示,注射药物4 h后BPQD-EMNVs在肿瘤部位富集程度最高,再经808 nm近红外光照射10 min后,BPQD-EMNVs能有效杀死肿瘤组织。结论本研究建立的BPQD-EMNVs制备方法简便,制得的BPQD-EMNVs具有良好的生物相容性和光热治疗效果,有望成为治疗乳腺癌的一种新手段。

Objective To investigate the method of preparing black phosphrous quantum dot (BPQD)-loaded erythrocyte membrane nanovesicles (BPQD-EMNVs), and to study its efficiency in photothermal therapy for breast cancer. Methods Fresh red blood cells (RBCs) of healthy mice were extracted to prepare erythrocyte membrane, and BPQD-EMNVs were prepared by sonication method. The morphology of BPQD-EMNVs was observed by a transmission electron microscopy. The particle size distribution was measured by a nano-particle size and Zeta potential meter. The encapsulation efficiency of BPQD was determined by inductively coupled plasma emission spectrometry. The uptake rate of BPQD-EMNVs was observed by a laser scanning confocal microscope. 4T1 tumor-bearing Balb/c mice were randomly divided into PBS, EMNVs, BPQD and BPQD-EMNVs groups, and the tumor sites were irradiated with 808 nm near-infrared light for 10 min after 4 hours of tail vein injection. The growth of the tumors was continually observed. Results The prepared BPQD-EMNVs have a regular spherical shape with an average particle diameter of 228 nm and an encapsulation efficiency of about 47%. Cellular uptake in vitro experiments showed that BPQD-EMNVs were rapidly taken up by 4T1 tumor cells. The results of animal in vivo experiments showed that BPQD-EMNVs had the highest enrichment after 4 h of injection at the tumor site, and BPQD-EMNVs could effectively kill tumor tissues after 10 min of 808 nm near-infrared light irradiation. Conclusions The BPQD-EMNVs are easy to prepare, and the prepared nanovesicles have good biocompatibility and photothermiotherapy effect, which is expected to be a promising method for breast cancer therapy.