Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
Biomaterials. 2012 Jun;33(18):4576-88. doi: 10.1016/j.biomaterials.2012.02.059. Epub 2012 Mar 23.
An optimized, biodegradable, dual temperature- and pH-responsive micelle system conjugated with functional group Cy5.5 was prepared in order to enhance tumor accumulation. The Dynamic light scattering (DLS) measurements showed that these diblock copolymers form micelle in PBS buffer with a size of around 50 nm by heating of an aqueous polymer solution from below to above the cloud point (CP). Anticancer drug, doxorubicin was incorporated into the inner core of micelle by hot shock protocol. The size and stability of the micelle were controlled by the copolymer composition and is fine tuned to extracellular pH of tumor. The mechanism then caused pH change and at body temperature which induce doxorubicin release from micelles and have strong effects on the viability of HeLa, ZR-75-1, MCF-7 and H661 cancer cells. Our in vivo results revealed a clear distribution of Doxorubicin-loaded mixed micelle (Dox-micelle) and efficiency targeting tumor site with particles increasing size in the tumor interstitial space, and the particles could not diffuse throughout the tumor matrix. In vivo tumor growth inhibition showed that Dox-micelle exhibited excellent antitumor activity and a high rate of anticancer drug in cancer cells by this strategy.
为了增强肿瘤积累，制备了一种与功能基团 Cy5.5 偶联的优化的、可生物降解的、双温度和 pH 响应性胶束系统。动态光散射（DLS）测量表明，这些两亲嵌段共聚物通过将水聚合物溶液从低于浊点（CP）加热到高于浊点，在 PBS 缓冲液中形成尺寸约为 50nm 的胶束。通过热冲击方案将抗癌药物阿霉素掺入胶束的内核中。胶束的尺寸和稳定性由共聚物组成控制，并通过微调与肿瘤细胞外 pH 相匹配。然后，该机制导致 pH 变化和体温变化，从而使阿霉素从胶束中释放，并对 HeLa、ZR-75-1、MCF-7 和 H661 癌细胞的活力产生强烈影响。我们的体内结果表明，载有阿霉素的混合胶束（Dox-micelle）的分布清晰，并且颗粒在肿瘤间质空间中增加尺寸，靶向肿瘤部位的效率高，颗粒不能扩散到整个肿瘤基质中。体内肿瘤生长抑制表明，通过这种策略，Dox-micelle 表现出优异的抗肿瘤活性和癌细胞中抗癌药物的高比率。
