Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210, USA.
Int J Nanomedicine. 2019 Oct 3;14:8001-8011. doi: 10.2147/IJN.S226798. eCollection 2019.
The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance.
In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The p value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility.
The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX.
All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.
开发能够高效地将抗癌药物包裹并递送到肿瘤部位，并能根据癌症治疗的特定信号提供载药可控释放的生物相容性纳米载体具有重要意义。
在这项工作中，我们制备了由两亲性聚合物聚乙二醇甲基醚接枝二硫键-聚（-氨基酸酯）（PBAE-ss-mPEG）和聚乙二醇化脂质自组装而成的混合脂质-聚合物纳米粒（LPNPs），用作药物递送载体。通过分析粒径、多分散指数（PDI）、细胞摄取、血清稳定性和载药能力，对聚乙二醇化脂质修饰进行了优化。LPNPs 的 p 值为 6.55，表明其具有 pH 敏感性。研究了 LPNPs 在不同 pH 值下的临界胶束浓度（CMC）值和 ζ 电位，以确认其 pH 敏感性。用还原剂孵育前后的 LPNPs 的形态用图像进行了研究，以研究其还原响应性。
体外结果表明，药物可以通过低 pH 值和高浓度还原剂触发从 LPNPs 中进行控制释放。此外，LPNPs 的细胞毒性非常低，与游离 DOX 相比，载阿霉素（DOX）的 LPNPs 能够有效地诱导肿瘤细胞死亡。
所有结果表明，所制备的 LPNPs 可以作为具有 pH/还原触发药物释放特征的潜在抗癌药物递送载体，而聚乙二醇化脂质修饰可能是制备药物递送平台的一种有用方法。
