Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging.
Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging.
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DOI：
10.3389/fonc.2020.563932
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发表时间：
2020
影响因子：
4.7
通讯作者：
Luo L
中科院分区：
文献类型：
--
作者：
Huang C;Liang J;Ma M;Cheng Q;Xu X;Zhang D;Shi C;Shang N;Xiao Z;Luo L
纳米给药系统是肿瘤精确治疗的一个重要研究领域，但对纳米给药系统治疗后微环境变化的研究较少。本研究旨在利用功能性磁共振成像技术检测阿霉素（DOX）-环甘氨酸-天冬氨酸多肽修饰的聚乳酸-羟基乙酸共聚物纳米系统（cRGD-PLGA@DOX）治疗肺癌移植瘤模型后血流动力学和微环境的变化。将32只荷瘤小鼠随机分为4组。A组用0.9%盐水处理，B组用4 mg/kg阿霉素处理，C组用2 mg/kg cRGD-PLGA@DOX处理，D组用4 mg/kg cRGD-PLGA@DOX处理。分别于治疗前及治疗后1、2、3周行体素内非相干运动弥散加权成像（IVIM-DWI）和R2弥散加权成像，测量D弥散、f、D和R2弥散值。检查后处死动物进行病理学检查。重建的cRGD-PLGA@DOX是均匀的，分散良好的，并且形状为球形，平均尺寸为180 nm。D组肿瘤体积最小，3周抑瘤率最高。B、C、D组的D值在3周内均呈上升趋势，D组上升幅度最大。除D组外，A、B、C组的D_（max）值与f值在3周内呈相似的增加趋势。A组的R2 β值在3周内逐渐升高，而各治疗组的趋势则相反。D值与Ki-67表达呈显著负相关（r =-0.757，P < 0.001），但与TUNEL（r = 0.621，P < 0.001）和10号染色体磷酸盐和张力同源性缺失（PTEN）染色呈阳性（r = 0.57，P = 0.004）。R2 α值与HIF-1a密切相关（r = 0.721，P < 0.001）。纳米药物表现出增强的抗肿瘤作用，而不需要增加化疗剂量。通过IVIM-DWI和R2 MR成像两种功能性MRI可以无创地检测治疗过程中肿瘤微环境如细胞和灌注的变化。
Nano-drug delivery system is an interesting field in precise cancer treatment, but few study has reported the microenvironmental changes after such treatment. This study aimed to detect the hemodynamic and microenvironmental changes in a lung cancer xenograft model after treated with doxorubicin (DOX) encapsulated by a cyclic arginine-glycine-aspartic acid polypeptide modified poly-(lactic-co-glycolic acid) nanosystem (cRGD-PLGA@DOX) using functional magnetic resonance imaging. Thirty-two tumor-bearing mice were randomly divided into four groups. Group A was treated with 0.9% saline, Group B with 4 mg/kg of doxorubicin, Group C with 2 mg/kg of cRGD-PLGA@DOX, and Group D with 4 mg/kg of cRGD-PLGA@DOX. Intravoxel incoherent motion diffusion-weighed imaging (IVIM-DWI) and R2∗ mapping were performed, and D∗, f, D, and R2∗ values were obtained before and1, 2, and 3 weeks after treatment. They were sacrificed for pathological examination after examinations. The reconstructed cRGD-PLGA@DOX was homogeneous, well-dispersed, and spherical in shape, with an average size of 180 nm. Group D demonstrated the smallest tumor volume and highest tumor inhibition rate in 3 weeks. D value of Group B, C, and D manifested an upward trend in 3 weeks with the highest increase in Group D. D∗ values shared a similar increased trends with f values in Group A, B, and C in 3 weeks, except Group D. R2∗ value of Group A gradually increased in 3 weeks, but the trends were reversed in the treatment groups. D value was significantly negative with Ki-67 expression (r = −0.757, P < 0.001) but positive with TUNEL (r = 0.621, P < 0.001), and phosphate and tension homology deleted on chromosome ten (PTEN) staining (r = 0.57, P = 0.004). R2∗ value was closely correlated with HIF-1a (r = 0.721, P < 0.001). The nano-drug demonstrated an enhanced anti-tumor effect without the need of increased chemotherapeutic dosage. The tumor microenvironment such as cellular and perfusion changes during treatment can be non-invasively detected by two functional MRI including IVIM-DWI and R2∗ mapping.
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影响因子：
5
作者：
Liang, Jianye;Mae, Rong;Luo, Liangping
通讯作者：
Luo, Liangping
精确交付用于 MRI 引导癌症治疗的多功能纳米系统，并通过功能扩散加权 MRI 监测肿瘤反应
影响因子：
7
作者：
Xiao, Zeyu;Chan, Leung;Luo, Liangping
通讯作者：
Luo, Liangping
影响因子：
11.2
作者：
Shi, Changzheng;Liu, Dexiang;Luo, Liangping
通讯作者：
Luo, Liangping
通过非对比体素内不相干运动扩散加权 MRI 监测恩度诱导的肿瘤血管正常化过程
影响因子：
4.7
作者：
Pan JH;Zhu S;Huang J;Liang J;Zhang D;Zhao X;Ding H;Qin L;Shi C;Luo L;Pan Y
通讯作者：
Pan Y
影响因子：
64.8
作者：
JOHNSON, DG;SCHWARZ, JK;NEVINS, JR
通讯作者：
NEVINS, JR