聚(对氧环己酮-co-l-苯丙氨酸氮芥)纳米颗粒用于乳腺癌移植瘤治疗

Poly(p-dioxanone-co-l-melphalan)nanoparticles for the treatment of breast cancer xenografts

目的:探讨具有缓释功能的聚(对氧环己酮-co-l-苯丙氨酸氮芥)静电喷雾纳米颗粒(PDCM NP)对乳腺癌细胞及裸鼠移植瘤的增殖抑制作用。方法:不同l-苯丙氨酸氮芥含量的PDCM NP分别与人乳腺癌细胞MCF-7共同培养1、3、5、7 d后观察PDCM NP对细胞增殖的影响。荧光标记的PDCM NP与MCF-7细胞共同培养24 h后在荧光显微镜下观察MCF-7对PDCM NP的吞噬情况。0.1 mL 10 mg/mL的PDCM-2 NP混悬液用于治疗皮下种植MCF-7细胞的移植瘤裸鼠20 d,期间测量、记录肿瘤体积变化。20 d后处死,肿瘤组织进行苏木精-伊红染色(HE)、TUNEL染色以统计瘤内细胞坏死、凋亡状况。结果:PDCM NP可抑制MCF-7细胞增殖,其抑制能力与PDCM所含l-苯丙氨酸氮芥量成正比,另外PDCM NP可被MCF-7吞噬,单次瘤内注射PDCM NP可有效抑制MCF-7移植瘤的增殖。结论:PDCM NP可有效抑制MCF-7细胞及其裸鼠移植瘤的增殖。

Objective:To investigate the suppressive effect of poly(p-dioxanone-co-l-melphalan)nanoparticles(PDCM NP)on breast cancer cells in vitro and xenograft in vivo.Methods:PDCM NP with different content of l-melphalan was prepared to culture with MCF-7 cells for 1,3,5,7 d and then the effect of PDCM NP on cell proliferation was observed.Subsequently,fluorescence labeling PDCM NP was cultured with MCF-7 cells to investigate the phagocytosis of MCF-7 cells on these NPs.At last,the MCF-7 xenograft models on nude mice were established and 0.1 mL 10 mg/mL PDCM-2 NP was used to treat nude mice for 20 d.The tumor size was measured and recorded during 20 d.After that,the mice were sacrificed and the xenografts were stained with hematoxylin-eosin(HE)and TdT-mediated dUTP Nick-End Labeling(TUNEL)to observe the necrosis and apoptosis conditions of the cell in tumor.Results:PDCM NP suppressed the proliferation of MCF-7 cells in vitro,and the suppression efficiency increased with the l-melphalan content in PDCM.PDCM NP could be phagocytosed by MCF-7 cells.In addition,PDCM NPs could suppress the proliferation of MCF-7 xenograft with single intratumor injection.Conclusion:PDCM NPs can suppress the proliferation of human breast cancer MCF-7 cells in vitro and its xenografts in vivo effectively.