Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
Biomater Sci. 2016 Jun 24;4(6):958-69. doi: 10.1039/c6bm00189k. Epub 2016 Apr 18.
An inherent dilemma in the use of nanomedicines for cancer drug delivery is their limited penetration into tumors due to their large size. We have demonstrated that dendrimer/lipid nanoassemblies can solve this problem by means of tumor-triggered disassembly and the release of small (several nanometers) dendrimers to facilitate tumor penetration. Herein, we report a general strategy for the fabrication of nanoassemblies from hydrophobic and hydrophilic dendrimers with phospholipids. Hydrophobic dendrimers could assemble with lipids via hydrophobic interactions, whereas hydrophilic dendrimers could only assemble with lipids in the presence of anionic surfactants via both electrostatic and hydrophobic interactions. The nanoassemblies of hydrophobic dendrimers/lipids were found to be capable of stripping off their lipid layers via fusion with the cell membrane and then intracellular or extracellular release of dendrimers, whereas the nanoassemblies of hydrophilic dendrimers/lipids were internalized via endocytosis and then released their dendrimers inside the cells. Therefore, these dendrimer/lipid nanoassemblies could be used for the delivery of different cancer drugs.
纳米医学在癌症药物传递中的应用存在一个固有难题，即由于其尺寸较大，其进入肿瘤的能力有限。我们已经证明，通过肿瘤触发的解组装和释放小（几纳米）的树枝状聚合物来促进肿瘤穿透，树枝状聚合物/脂质纳米组装体可以解决这个问题。在此，我们报告了一种使用疏水性和亲水性树枝状聚合物与磷脂制备纳米组装体的通用策略。疏水性树枝状聚合物可以通过疏水相互作用与脂质组装，而亲水性树枝状聚合物只能在阴离子表面活性剂存在的情况下通过静电和疏水相互作用与脂质组装。发现疏水性树枝状聚合物/脂质的纳米组装体能够通过与细胞膜融合而脱去其脂质层，然后在细胞内或细胞外释放树枝状聚合物，而亲水性树枝状聚合物/脂质的纳米组装体则通过内吞作用内化，并在细胞内释放其树枝状聚合物。因此，这些树枝状聚合物/脂质纳米组装体可用于递送不同的癌症药物。
