Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
J Control Release. 2010 Jun 1;144(2):259-66. doi: 10.1016/j.jconrel.2010.02.024. Epub 2010 Feb 24.
Herein, we evaluated the tumoral low pH targeting characteristics of pH-responsive polymer micelles in cancer targeting therapy. To design the pH-responsive polymeric micelles, hydrophilic methyl ether poly(ethylene glycol) (MPEG) and pH-responsive/biodegradable poly(beta-amino ester) (PAE) were copolymerized using a Michael-type step polymerization, resulting in an MEPG-PAE block copolymer. The amphiphilic MPEG-PAE block copolymer formed polymeric micelles with nano-sized diameter by self-assembly, which showed a sharp pH-dependant micellization/demicellization transition at the tumoral acidic pH value (pH 6.4). For the cancer image and therapy, fluorescence dye, tetramethylrhodamine isothiocyanate (TRITC), or anticancer drug, camptothecin (CPT), was efficiently encapsulated into the pH-responsive polymeric micelles (pH-PMs) by a simple solvent casting method. The TRITC or CPT encapsulated pH-PMs (TRITC-pH-PMs or CPT-pH-PMs) showed rapid release of TRITC or CPT in weakly acidic aqueous (pH 6.4) because they still presented a sharp tumoral acid pH-responsive micellization/demicellization transition. The pH-PMs with 10wt.% of TRITC could deliver substantially more fluorescence dyes to the target tumor tissue in MDA-MB231 human breast tumor-bearing mice, compared to the control polymeric micelles of PEG-poly(l-lactic acid) (PEG-PLLA). Importantly, CPT-pH-PMs exhibited significantly increased therapeutic efficacy with minimum side effects by other tissues in breast tumor-bearing mice, compared to free CPT and CPT encapsulated PEG-PLLA micelles. The tumoral acidic pH-responsive polymeric micelles are highly useful for cancer targeting therapy.
在此，我们评估了 pH 响应聚合物胶束在癌症靶向治疗中的肿瘤低 pH 靶向特性。为了设计 pH 响应聚合物胶束，使用迈克尔型逐步聚合将亲水性甲醚聚乙二醇（MPEG）和 pH 响应/可生物降解的聚（β-氨基酯）（PAE）共聚，得到 MEPG-PAE 嵌段共聚物。两亲性 MPEG-PAE 嵌段共聚物通过自组装形成纳米尺寸的聚合物胶束，在肿瘤酸性 pH 值（pH 6.4）下表现出明显的 pH 依赖性胶束化/去胶束化转变。对于癌症成像和治疗，荧光染料四甲基罗丹明异硫氰酸酯（TRITC）或抗癌药物喜树碱（CPT）通过简单的溶剂浇铸法被有效包封到 pH 响应聚合物胶束（pH-PMs）中。TRITC 或 CPT 包封的 pH-PMs（TRITC-pH-PMs 或 CPT-pH-PMs）在弱酸性水（pH 6.4）中迅速释放 TRITC 或 CPT，因为它们仍呈现出明显的肿瘤酸性 pH 响应胶束化/去胶束化转变。与对照 PEG-聚（L-乳酸）（PEG-PLLA）聚合物胶束相比，载有 10wt.%TRITC 的 pH-PMs 能够将更多的荧光染料递送到 MDA-MB231 人乳腺癌荷瘤小鼠的靶肿瘤组织中。重要的是，CPT-pH-PMs 在乳腺癌荷瘤小鼠的其他组织中表现出显著增加的治疗效果，同时副作用最小，与游离 CPT 和 CPT 包封的 PEG-PLLA 胶束相比。肿瘤酸性 pH 响应聚合物胶束对癌症靶向治疗非常有用。
