Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine

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Abstract

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.

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Sun, W., Ji, W., Hu, Q., Yu, J., Wang, C., Qian, C., … Gu, Z. (2016). Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine. Biomaterials, 96, 1–10. https://doi.org/10.1016/j.biomaterials.2016.04.011

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