Development of Halofluorochromic Polymer Nanoassemblies for the Potential Detection of Liver Metastatic Colorectal Cancer Tumors Using Experimental and Computational Approaches.
Development of Halofluorochromic Polymer Nanoassemblies for the Potential Detection of Liver Metastatic Colorectal Cancer Tumors Using Experimental and Computational Approaches.
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DOI：
10.1007/s11095-017-2245-9
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发表时间：
2017-11
影响因子：
3.7
通讯作者：
Bae Y
中科院分区：
文献类型：
--
作者：
Reichel D;Curtis LT;Ehlman E;Mark Evers B;Rychahou P;Frieboes HB;Bae Y
开发用卤代荧光染料修饰的聚合物纳米组装体（PNA），以允许检测肝转移性结直肠癌（CRC），从而改善治疗结果。我们结合联合收割机的实验和计算方法，以评估宏观和微观PNA分布在患者来源的异种移植原发性和正交异性肝转移性CRC肿瘤。由聚（乙二醇）、荧光染料（尼罗蓝、Alexa 546和IR 820）和疏水基团（棕榈酸酯）制备卤代荧光变色和非卤代荧光变色PNA（hfPNA和n-hfPNA），所有这些均共价连接到阳离子聚合物支架[聚（乙烯亚胺）或聚（赖氨酸）]上，形成平均直径< 30 nm的颗粒。染料缀合的PNA在调理条件下24小时未显示聚集，并显示低组织扩散和细胞摄取。静脉注射后12小时内，hfPNA和n-hfPNA在原发性和肝转移性CRC肿瘤中积累。与n-hfPNA相比，hfPNA仅在酸性肿瘤微环境（pH<7.0）中发出强烈荧光，并将小的转移性CRC肿瘤与健康的肝基质区分开。计算模拟显示，PNA将稳定地积累主要是在酸性（缺氧）的转移性肿瘤，独立于周围组织的血管化程度的病变。结合的实验和计算数据证实，检测酸性肿瘤组织的hfPNA可用于以提高的准确性鉴定小的肝转移性CRC肿瘤。
To develop polymer nanoassemblies (PNAs) modified with halofluorochromic dyes to allow for the detection of liver metastatic colorectal cancer (CRC) to improve therapeutic outcomes. We combine experimental and computational approaches to evaluate macroscopic and microscopic PNA distributions in patient-derived xenograft primary and orthotropic liver metastatic CRC tumors. Halofluorochromic and non-halofluorochromic PNAs (hfPNAs and n-hfPNAs) were prepared from poly(ethylene glycol), fluorescent dyes (Nile blue, Alexa546, and IR820), and hydrophobic groups (palmitate), all of which were covalently tethered to a cationic polymer scaffold [poly(ethylene imine) or poly(lysine)] forming particles with an average diameter < 30 nm. Dye-conjugated PNAs showed no aggregation under opsonizing conditions for 24 h and displayed low tissue diffusion and cellular uptake. Both hfPNAs and n-hfPNAs accumulated in primary and liver metastatic CRC tumors within 12 h post intravenous injection. In comparison to n-hfPNAs, hfPNAs fluoresced strongly only in the acidic tumor microenvironment (pH<7.0) and distinguished small metastatic CRC tumors from healthy liver stroma. Computational simulations revealed that PNAs would steadily accumulate mainly in acidic (hypoxic) interstitium of metastatic tumors, independently of the vascularization degree of the tissue surrounding the lesions. The combined experimental and computational data confirms that hfPNAs detecting acidic tumor tissue can be used to identify small liver metastatic CRC tumors with improved accuracy.
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影响因子：
17.1
作者：
Kumar R;Roy I;Ohulchanskky TY;Vathy LA;Bergey EJ;Sajjad M;Prasad PN
通讯作者：
Prasad PN
DOI：
10.1016/j.jconrel.2013.09.013
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
通讯作者：
Li SD
DOI：
10.3109/02656736.2013.817615
发表时间：
2013-08
期刊：
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
影响因子：
--
作者：
Barnes KD;Shafirstein G;Webber JS;Koonce NA;Harris Z;Griffin RJ
通讯作者：
Griffin RJ
影响因子：
4.3
作者：
Kekelidze, Maka;D'Errico, Luigia;Hohmann, Joachim
通讯作者：
Hohmann, Joachim
影响因子：
6.2
作者：
Lee, Hyun Jin;Bae, Younsoo
通讯作者：
Bae, Younsoo