In situ protein-templated porous protein-hydroxylapatite nanocomposite microspheres for pH-dependent sustained anticancer drug release.
In situ protein-templated porous protein-hydroxylapatite nanocomposite microspheres for pH-dependent sustained anticancer drug release.
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原位蛋白质模板多孔蛋白质-羟基磷灰石纳米复合微球用于pH依赖性持续抗癌药物释放
DOI：
10.1039/c7tb00208d
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发表时间：
2017-06-07
期刊：
影响因子：
--
通讯作者：
Yang M
中科院分区：
文献类型：
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作者：
Shuai Y;Yang S;Li C;Zhu L;Mao C;Yang M
蚕丝胶蛋白是一种水溶性胶样蛋白，具有生物相容性、亲水性、可降解性和资源丰富等优点，被广泛用作生物材料。此外，基于羟基磷灰石的药物载体由于其生物可降解性、生物相容性和易于体内代谢而在功能上有效地用于药物或基因递送。在此，本研究首次使用了来自一种名为Antheraea pernyi（A. pernyi）作为模板，使羟基磷灰石（HAp）纳米针成核，并形成作为抗癌药物载体的多孔绢云母-HAp纳米复合微球。具体地说，A.将柞蚕丝胶蛋白（AS）在1.5× 10 ~（-1）的模拟体液中原位诱导形成AS/HAp多孔微球。阿霉素（DOX）载药和释放实验证明，该微球具有pH依赖性的DOX控释和缓释作用。特别地，微球可以在肿瘤微环境典型的酸性条件下比在正常组织典型的生理条件下以更高的速率选择性地释放DOX，这将潜在地减少癌症药物在正常组织中的副作用。癌细胞毒性测定、癌细胞成像和细胞内DOX分布测定提供了进一步的证据来支持DOX从微球向癌细胞的pH依赖性控制和持续释放。我们的工作已经证明了设计和合成丝蛋白为基础的药物载体，可以潜在地用于药物输送和再生医学的仿生策略。通过在1.5SBF溶液中孵育，制备了具有多孔结构和pH依赖性药物释放特性的蛋白质-羟基磷灰石微球。
Silk sericin, a water-soluble glue-like protein, is extensively used as a biomaterial due to its biocompatibility, hydrophilicity, biodegradability, and adequate resource. In addition, hydroxyapatite-based drug carriers are functionally efficient for drug or gene delivery due to their biodegradability, biocompatibility and easy metabolism in vivo. Herein, for the first time, this study used sericin, from a wild silkworm called Antheraea pernyi (A. pernyi), as a template to nucleate hydroxylapatite (HAp) nano-needles and form porous sericin-HAp nanocomposite microspheres as an anticancer drug carrier. Specifically, A. pernyi sericin (AS) was incubated in 1.5× simulated body fluid to induce the formation of porous AS/HAp microspheres in situ. Doxorubicin (DOX) loading and release assays proved that the microspheres exhibited pH-dependent controlled and sustained release of DOX. In particular, the microspheres can selectively release DOX at a higher rate at the acidic conditions typical for tumor microenvironment than at the physiological conditions typical for normal tissues, which will potentially reduce the side effect of the cancer drugs in normal tissues. Cancer cell toxicity assay, cancer cell imaging and intracellular DOX distribution assay provided further evidence to support the pH-dependent controlled and sustained release of DOX to cancer cells from the microspheres. Our work has demonstrated a biomimetic strategy for the design and synthesis of silk protein-based drug carriers that can be potentially employed in drug delivery and regenerative medicine. Protein-hydroxylapatite microspheres with a porous structure and a pH-dependent drug release profile are fabricated by incubating sericin in 1.5 SBF solution.