Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China.
Biomater Sci. 2016 Nov 15;4(12):1802-1813. doi: 10.1039/c6bm00504g.
To increase the accumulation of nanocarriers at the tumor site and reduce premature drug leakage, we fabricated alginate modified superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic targeting capability for pH-responsive release of the anticancer drug doxorubicin (DOX) in tumor-cell microenvironments. The drug loading content (DLC) of SPION-4 was as high as 48.98% with a stable size of 135 nm, whereas the DLC of SPION-2 (amine-functionalized SPIONs as the control) was 7.58%. The in vitro release studies revealed that the acidic environment (pH 6.5 and pH 5.0) triggered the effective release of DOX from DOX-loaded SPION-4 twice and thrice as much as the neutral condition (pH 7.4) after 10.7 h, respectively. These nanocarriers exhibited good cytocompatibility towards both normal cells (LO2) and cancer cells (HepG2), but higher cytotoxicity against HepG2 cells for DOX-loaded SPION-4 than that against LO2 cells could be observed due to the effects of an additional magnet and the acidic microenvironment of cancer cells, which greatly improved the cellular uptake of magnetic nanoparticles and released more DOX in the cytoplasm and nucleus. The in vivo biodistribution and anti-tumor efficacy demonstrated that DOX-loaded SPION-4 under an external magnetic field could obviously increase the DOX concentration in tumor tissues to remarkably inhibit tumor growth and significantly reduce side effects of free DOX. Therefore, this work suggested that these SPION-4 nanoparticles may be a potential carrier to deliver chemotherapeutic agents in anti-tumor treatment.
为了增加纳米载体在肿瘤部位的积累并减少药物的过早泄漏，我们制备了具有磁靶向能力的海藻酸盐修饰的超顺磁性氧化铁纳米粒子（SPIONs），用于在肿瘤细胞微环境中响应 pH 值释放抗癌药物阿霉素（DOX）。SPION-4 的载药量（DLC）高达 48.98%，粒径稳定在 135nm，而 SPION-2 的 DLC（作为对照的胺功能化 SPIONs）为 7.58%。体外释放研究表明，酸性环境（pH 6.5 和 pH 5.0）分别在 10.7 小时后触发 DOX 从 DOX 负载的 SPION-4 中的有效释放，是中性条件（pH 7.4）的两倍和三倍。这些纳米载体对正常细胞（LO2）和癌细胞（HepG2）均表现出良好的细胞相容性，但对于 DOX 负载的 SPION-4，由于外加磁场和癌细胞酸性微环境的影响，对 HepG2 细胞的细胞毒性明显高于 LO2 细胞，可以观察到更高的细胞毒性，这大大提高了磁性纳米颗粒的细胞摄取能力，并在细胞质和核内释放了更多的 DOX。体内分布和抗肿瘤功效表明，在外磁场下负载 DOX 的 SPION-4 可明显增加肿瘤组织中的 DOX 浓度，显著抑制肿瘤生长，并显著降低游离 DOX 的副作用。因此，这项工作表明，这些 SPION-4 纳米粒子可能是一种潜在的载体，可用于抗肿瘤治疗中输送化疗药物。
