Double-Lock Nanomedicines Enable Tumor-Microenvironment-Responsive Selective Antitumor Therapy |
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Authors: | Fang Liu Jundong Zhu Peipei Dai Jian Deng Juan Qin Zhiguang Yuchi Aiping Fan Zheng Wang Yanjun Zhao |
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Affiliation: | School of Pharmaceutical Science and Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072 P. R. China |
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Abstract: | A hybrid nanocarrier for reducing the off-target adverse effects of chemotherapy via selective drug delivery to the tumor cells is reported. The model active agent, combretastatin A4 (CA4) phosphate is deposited onto the magnetite (Fe3O4) nanoparticles as the core, followed by lipid coating as the shell. Upon nanocarrier administration and biodistribution to the tumor site, the high level of adenosine triphosphate in the extracellular space of tumor induces the cargo release via phosphate displacement. Then, the CA4 phosphate is dephosphorylated by the alkaline phosphatase that is overexpressed at the plasma membrane of certain tumor cells, resulting in enhanced intracellular uptake of hydrophobic CA4. These sequential two-step unlocking processes enable the preferable accumulation of CA4 within tumor cells. Such approach is applicable to a wide range of chemotherapeutics and is promising for efficacy enhancement and side-effect reduction of antitumor chemotherapy. |
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Keywords: | adenosine triphosphate alkaline phosphatase cancer nanomedicine drug delivery stimuli-responsive |
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