分會

第四十五分會：納米生物分析與納米藥物化學(xué)

摘要

Currently, cell membrane was always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular certain therapeutic mechanism might deserve full credit as an effective means in cancer treatment. In this study, we developed an antitumor nanoreactor which replicated the specific killing mechanism in hypoxic red blood cells (RBC). The nanoplatform was formulated based on hollow mesoporous TiO2 nanoparticles by hemoglobin (Hb) modification, model drug (RRx-001) loading and then cancer cell membrane (CCM) coating. The CCM-Hb-TiO2/RRx-001 mimicked both the surface properties of CCM and the intracellular certain therapeutic mechanism in RBC, which could homologous target the tumor cells and transfer the battlefield from hypoxic RBC to hypoxic tumor cells. Importantly, hemoglobin (Hb) as a natural protein in RBC played a dual role in this nanoreactor, since it had oxygen carrying capability and nitrite reductase activity in its oxy- and deoxy-state, respectively. Once the Hb was deoxygenated in the battlefield of hypoxic tumor, the biomimetic nanoreactor was activated and triggered a series of reactions in cascade and specific fashion. The oxygen compensation from Hb enhanced TiO2 mediated reactive oxygen species (ROS) generation for sonodynamic therapy. Meanwhile, the nitrite reductase activity of deoxy-Hb was potentiated by RRx-001 and drove nitric oxide (NO) generation. Subsequently, the resulted reactive nitrogen species (RNS) were highly active and brought out deleterious consequences in cell damage for tumor therapy. Based on the above findings, it was undoubtedly logical that such biomimetic nanoreactor (CCM-Hb-TiO2/RRx-001) certainly would bring out the remarkable antitumor effect based on battlefield transfer strategy.

關(guān)鍵詞

biomimetic;hemoglobin;nitrite reductase activity;oxygen-carrying capability

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