Self-Regulated Multifunctional Collaboration of Targeted Nanocarriers for Enhanced Tumor Therapy
Self-Regulated Multifunctional Collaboration of Targeted Nanocarriers for Enhanced Tumor Therapy
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靶向纳米载体的自我调节多功能协作增强肿瘤治疗。
DOI：
10.1021/bm5009348
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发表时间：
2014-10-01
影响因子：
6.2
通讯作者：
Shi, Linqi
中科院分区：
文献类型：
--
作者：
Gao, Hongjun;Cheng, Tangjian;Shi, Linqi
探索理想的纳米载体给药系统遇到了不可避免的障碍，特别是增强细胞摄取和延长血液循环之间的冲突，这决定了癌症治疗的最终效果。在此基础上，构建了基于可控自组装的表面结构对外部环境的响应变化，以克服冲突。通过双嵌段两亲共聚物的自组装，设计了一种具有亲水性聚乙二醇（PEG）和pH响应性疏水性聚β-氨基酯（PAE）混合壳的新型胶束。为了避免表面暴露的靶向组c（RGDfK）加速血液循环的清除，这里c（RGDfK）被偶联到疏水性PAE并在pH 7.4下隐藏在PEG的外壳中。根据HepG2细胞摄取实验，在肿瘤pH下，电荷转换发生，c（RGDfK）伸展出壳，促进细胞内化。同时，非均匀的表面结构使胶束具有延长血液循环的特性。通过增强细胞摄取和延长血液循环的自我调节多功能协同特性，在荷瘤小鼠模型中成功地实现了肿瘤生长的抑制。这种新型纳米载体在未来的临床实验中具有广阔的应用前景。
Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(β-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.