目的构建靶向胰腺癌的杂化癌细胞膜/中性粒细胞膜伪装聚多巴胺螯合锰(Ⅱ)纳米探针(PMNP@FMs)，探讨其用于胰腺癌荧光成像及MRI的潜力。
方法将癌细胞膜与中性粒细胞膜融合，包覆在螯合锰(Ⅱ)的聚多巴胺纳米粒子(PMNPs)表面，获得PMNP@FMs，检测其形貌结构及MRI性能等。用细胞计数试剂盒(CCK)－8检测PMNP@FMs对人胰腺癌细胞PANC－1和正常人胰腺导管上皮细胞hTERT－HPNE的细胞毒性，并检测PMNP@FMs对正常小鼠的活体毒性。构建PANC－1胰腺癌荷瘤裸鼠模型，行小动物活体荧光成像和MRI。采用两独立样本 t检验、重复测量方差分析及最小显著差异法进行组间比较。
结果PMNP@FMs呈核壳结构，粒径为(112.81±8.64) nm，具有负电位，且分散性良好。PMNPs的T 1弛豫效率是钆喷酸二甲葡胺(Gd－DTPA)的4.1倍(18.81±0.22与4.55±0.24； t＝75.54， P<0.001)。与正常人胰腺导管上皮细胞hTERT－HPNE和人源胰腺癌细胞PANC－1共培养24 h后，在0～500 μg/ml范围内，PMNPs和PMNP@FMs处理过的细胞存活率均大于90%，且PMNP@FMs对小鼠存活无影响，未发现明显脏器损害。小动物MRI及荧光成像显示，PMNP@FMs在静脉给药后24 h高度聚集于肿瘤并达到峰值，相对MR信号值和荧光强度分别为1.35±0.01和(1.20±0.25)×10 10，明显高于对照组的峰值1.22±0.01和(3.87±0.50)×10 9( F值：11.53～188.01， t值：18.20、5.64，均 P<0.05)，且PMNP@FMs主要经肝脏代谢。
结论PMNP@FMs具有用于靶向胰腺癌荧光成像及MRI的潜能，有望为早期胰腺癌的精准诊断提供新方法。
ObjectiveTo construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.
MethodsCancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method.
ResultsPMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9; F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance.
ConclusionPMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.
钟妍其,马莹莹,卢文正,等. 双细胞膜仿生纳米探针用于胰腺癌荧光－MR双模态成像的研究[J]. 中华核医学与分子影像杂志,2025,45(02)：88-93.
DOI:10.3760/cma.j.cn321828-20240417-00134版权归中华医学会所有。
未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。
除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。
钟妍其：研究实施、论文撰写；马莹莹：研究实施；卢文正：统计学分析；陈荆晓、钱建瑛、王鹏、赵静：研究指导、论文修改；张衡、葛宇曦、胡曙东：研究指导、经费支持
文档即答
智问智答
机器翻译
你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。
