Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Biomaterials. 2013 Jan;34(2):552-61. doi: 10.1016/j.biomaterials.2012.09.065. Epub 2012 Oct 15.
Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)(4)-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice.
尽管通过配体修饰或肿瘤微环境敏感的纳米载体介导的靶向递送已被广泛用于癌症化疗，但由于系统给药后药物过早释放，其效率仍受到限制。在此，我们报告了一种由二硫键（DS）键合的 mPEG-（Cys）（4）-PDLLA 胶束制成的高度稳定的血液、肿瘤适应性药物载体。静脉注射的二硫键键合胶束在血液中稳定地保留阿霉素，并将药物有效地递送到肿瘤部位，与自组装（SA）、非交联的 mPEG-PDLLA 胶束相比，肿瘤内药物增加了 7 倍，心脏内药物减少了 1.9 倍。与自组装胶束给药相比，二硫键键合胶束给药后可使阿霉素在癌细胞核内积聚，而自组装胶束给药后则未观察到这一现象。在给予 2 毫克/千克的低剂量阿霉素后，二硫键键合胶束几乎完全抑制了小鼠的肿瘤生长。
