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Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine
- Sun, Wujin, Ji, Wenyan, Hu, Quanyin, Yu, Jicheng, Wang, Chao, Qian, Chenggen, Hochu, Gabrielle, Gu, Zhen
- Biomaterials 2016 v.96 pp. 1-10
- apoptosis, complementary DNA, cytokines, death domain receptors, endocytosis, ligands, models, nanocarriers, nanofibers, necrosis, neoplasm cells, neoplasms, phospholipase A2, plasma membrane
- Direct delivery of cytokines using nanocarriers holds great promise for cancer therapy. However, the nanometric scale of the vehicles made them susceptible to size-dependent endocytosis, reducing the plasma membrane-associated apoptosis signaling. Herein, we report a tumor microenvironment-responsive and transformable nanocarrier for cell membrane targeted delivery of cytokine. This formulation is comprised of a phospholipase A2 (PLA2) degradable liposome as a shell, and complementary DNA nanostructures (designated as nanoclews) decorated with cytokines as the cores. Utilizing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a model cytokine, we demonstrate that the TRAIL loaded DNA nanoclews are capable of transforming into nanofibers after PLA2 activation. The nanofibers with micro-scaled lengths efficiently present the loaded TRAIL to death receptors on the cancer cell membrane and amplified the apoptotic signaling with reduced TRAIL internalization.