Department of Radiology, Case Western Reserve University , Cleveland , Ohio Pluronic Structure and Function.
Int J Hyperthermia. 2011;27(7):663-71. doi: 10.3109/02656736.2011.599828.
To identify specific Pluronic triblock copolymer structural properties which are critical to its function as a sensitiser in hyperthermia treatment of experimental colorectal adenocarcinoma.
DHD/K12/TRb rat colorectal adenocarcinoma cells were exposed to Pluronics, a family of triblock copolymers with the general structure EO(x)-PO(y)-EO(x) (EO: ethylene oxide, and PO: propylene oxide), at a range of molecular weights (Mw) and EO:PO:EO sub-unit lengths and then submitted to sublethal heat (43°C) treatment. Outcomes indicating Pluronic performance as a thermal sensitiser were correlated with its structural properties; lead candidates were determined accordingly. Finally, one of the lead candidates, Pluronic L61, a 2000 Da copolymer, was used to assess sensitising functionality in vivo in a subcutaneous rat model of colorectal carcinoma.
Pluronics with 1100 ≤ Mw ≤ 3200 Da and hydrophilic lipophilic balance (HLB) between 1-8 demonstrated the highest thermosensitising ability. Pluronics L31, L61, L62, L10 and L64 were found to be among the most effective copolymers for hyperthermia sensitisation under tested conditions. Most encouraging, L61 in synergy with hyperthermia significantly reduced tumour growth progression in vivo compared to tumours treated with hyperthermia alone.
Pluronic copolymer structure properties including, Mw, HLB and PO length are essential to its hyperthermia sensitising function.
确定普朗尼克嵌段共聚物的特定结构特性，这些特性对其作为高热治疗实验性结直肠腺癌增敏剂的功能至关重要。
DHD/K12/TRb 大鼠结直肠腺癌细胞暴露于普朗尼克嵌段共聚物（EO(x)-PO(y)-EO(x) 的结构），该共聚物家族具有一系列分子量（Mw）和 EO:PO:EO 亚单位长度，并随后接受亚致死热（43°C）处理。指示普朗尼克作为热增敏剂性能的结果与结构特性相关联；相应地确定了候选药物。最后，选择其中一种候选药物，分子量为 2000 Da 的普朗尼克 L61，用于评估皮下结直肠癌细胞癌大鼠模型中体内的增敏功能。
Mw 为 1100≤Mw≤3200Da 且亲水亲油平衡（HLB）为 1-8 的普朗尼克表现出最高的热增敏能力。在测试条件下，发现普朗尼克 L31、L61、L62、L10 和 L64 是最有效的共聚物之一，可用于高热增敏。最令人鼓舞的是，L61 与高热协同作用可显著降低体内肿瘤生长进展，与单独接受高热治疗的肿瘤相比。
普朗尼克嵌段共聚物的结构特性，包括 Mw、HLB 和 PO 长度，对其高热增敏功能至关重要。
