CAJ | 학술논문

目的制备负载油性超顺磁性氧化铁(SPIO)、水性SPIO聚合物纳米囊泡,并观察负载油性SPIO、水性SPIO聚合物纳米囊泡对结肠癌的MR显像能力.方法通过多步化学反应制备聚乙二醇-聚D,L-丙交酯(PEG-PDLLA)纳米囊泡,并分别负载油性、水性SPIO.18只荷结肠癌裸鼠模型采用数字表法随机分为3组,每组6只,分别从尾静脉注射单纯SPIO水溶液、负载油性SPIO聚合物纳米囊泡和水性SPIO聚合物纳米囊泡,行MRI动态扫描观察肿瘤、肝脏、肌肉的T2WI信号和T2值.采用重复测量设计的方差分析比较3组间肿瘤、肝脏、肌肉的T2WI信号强度改变,两两比较采用Bonferroni法.结果静脉注射负载油性、水性SPIO聚合物纳米囊泡后引起肿瘤T2WI信号强度下降,两者引起肿瘤信号强度下降最大百分比分别为11.00%、11.40%;单纯SPIO水溶液未能引起肿瘤信号强度下降,3组间比较差异有统计学意义(F=10.96,P＜0.01),负载油性、水性SPIO聚合物纳米囊泡引起的信号强度下降比单纯SPIO水溶液明显(P＜0.05);而负载油性和水性SPIO聚合物纳米囊泡间的差异无统计学意义(P＞0.05).3种对比剂均引起肝脏T2WI信号强度下降,单纯SPIO水溶液、负载油性、水性SPIO聚合物纳米囊泡引起肝脏信号强度下降的最大百分比分别为32.85%、52.77%、56.89%,3组间比较差异有统计学意义(F=161.18,P＜0.01),负载油性、水性SPIO聚合物纳米囊泡引起的信号强度下降比单纯SPIO水溶液明显(P＜0.01);负载水性SPIO聚合物纳米囊泡比负载油性SPIO聚合物纳米囊泡引起的信号强度下降更明显(P＜0.01).3种对比剂均未引起肌肉组织的T2WI信号强度下降,测量各组间肌肉的信号强度改变的差异无统计学意义(F=0.59,P＞0.05).结论负载SPIO聚合物纳米囊泡在体内可以引起肿瘤的T2WI信号强度下降,可做为肿瘤显像的对比剂.
목적 제비부재유성초순자성양화철(SPIO)、수성SPIO취합물납미낭포,병관찰부재유성SPIO、수성SPIO취합물납미낭포대결장암적MR현상능력.방법 통과다보화학반응제비취을이순-취D,L-병교지(PEG-PDLLA)납미낭포,병분별부재유성、수성SPIO.18지하결장암라서모형채용수자표법수궤분위3조,매조6지,분별종미정맥주사단순SPIO수용액、부재유성SPIO취합물납미낭포화수성SPIO취합물납미낭포,행MRI동태소묘관찰종류、간장、기육적T2WI신호화T2치.채용중복측량설계적방차분석비교3조간종류、간장、기육적T2WI신호강도개변,량량비교채용Bonferroni법.결과 정맥주사부재유성、수성SPIO취합물납미낭포후인기종류T2WI신호강도하강,량자인기종류신호강도하강최대백분비분별위11.00%、11.40%;단순SPIO수용액미능인기종류신호강도하강,3조간비교차이유통계학의의(F=10.96,P＜0.01),부재유성、수성SPIO취합물납미낭포인기적신호강도하강비단순SPIO수용액명현(P＜0.05);이부재유성화수성SPIO취합물납미낭포간적차이무통계학의의(P＞0.05).3충대비제균인기간장T2WI신호강도하강,단순SPIO수용액、부재유성、수성SPIO취합물납미낭포인기간장신호강도하강적최대백분비분별위32.85%、52.77%、56.89%,3조간비교차이유통계학의의(F=161.18,P＜0.01),부재유성、수성SPIO취합물납미낭포인기적신호강도하강비단순SPIO수용액명현(P＜0.01);부재수성SPIO취합물납미낭포비부재유성SPIO취합물납미낭포인기적신호강도하강경명현(P＜0.01).3충대비제균미인기기육조직적T2WI신호강도하강,측량각조간기육적신호강도개변적차이무통계학의의(F=0.59,P＞0.05).결론 부재SPIO취합물납미낭포재체내가이인기종류적T2WI신호강도하강,가주위종류현상적대비제.
Objective To synthesize the hydrophobic supraparamagnetic ironic oxide(SPIO) loaded and hydrophilic SPIO loaded polymeric nano-vesicles and to investigate the feasibility of using hydrophobic SPIO loaded and hydrophilic SPIO loaded polymeric nano-vesicles to display the tumor in MRI in vivo through animal experiments. Methods The polymeric nano-vesicles were prepared from poly (D, L-lactic acid) (PDLLA) and poly (ethylene glycol) (PEG) by a multiple emulsion/solvent evaporation method.The hydrophobic SPIO and hydrophilic SPIO were loaded in the polymeric nano-vesicles respectively.Eighteen nude mice models with human colorectal carcinoma xenograft were established. They were divided equally into three groups (n = 6). The three groups of nude mice models were injected with water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle via the mice caudal vein respectively.Dynamic MRI scan were performed in all the mice models. T2WI signal intensity and T2 relaxation time were measured in the tumor, liver and muscle by using T2 mapping software. ANOVA of repeated measurement was used to analyze if there were significant differences of signal intensity changes among the three groups, while Bonferroni method was used for pair-wise comparison. Results On T2 WI, tumors showed decrease in signal intensity after hydrophobic or hydrophilic SPIO loaded polymeric nano-vesicle injection, while no signal intensity decrease was found in the tumor after water-soluble SPIO administration. The maximum percentage of signal intensity decrease in tumor caused by hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 11.00%, 11.40%, respectively. There was statistical significant difference of signal intensity changes among these three groups (F = 10. 96, P ＜ 0. 01). The decrease in signal intensity in the groups with hydrophilic or hydrophobic SPIO loaded polymeric nano-vesicles injection were more pronounced as compared with that of water-soluble SPIO (P ＜ 0. 05), but there was no significant difference in signal intensity decrease between the groups of hydrophilic and hydrophobic SPIO-loaded polymeric vesicles injection (P ＞0. 05). The three agents could lead to signal intensity decrease in the liver. The maximum percentage of signal intensity decrease in liver caused by water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 32. 85%, 52. 77%, 56. 89%, respectively. There was statistical significant difference between these groups (F = 161.18, P ＜ 0. 01) . The groups of injecting hydrophilic and hydrophobic SPIO loaded polymeric nano-vesicles had the more obvious signal decrease than the one with water-soluble SPIO (P ＜ 0. 01). Hydrophilic SPIO loaded polymeric nano-vesicles exhibited more signal intensity decrease than hydrophobic SPIO loaded polymeric nano-vesicles (P ＜ 0. 01). All three agents could not lead to T2WI signal decrease in the muscle, and there was no significant difference in signal change on T2 WI among three groups (F = 0. 59, P ＞ 0. 05). Conclusion SPIO loaded polymeric nano-vesicles can cause significant T2WI signal loss in human colonic carcinoma on MR imaging in vivo. It can be used as tumor imaging contrast agents.