Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Sci Rep. 2016 Jun 9;6:27559. doi: 10.1038/srep27559.
Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to αVβ3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Improved in vitro and in vivo tumor targeting and penetration were observed with NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD enhanced the accumulation and penetration of NCs in tumors. The NCs were cytocompatible, histocompatible, and non-toxic to other healthy tissues. The endocytosis of NCs was mediated by lipid rafts in an energy-dependent manner, leading to better cytotoxicity of PTX against cancer cells. In contrast with commercial product, PTX-loaded NCs (PTX-NCs) increased area under concentration-time curve (AUC) by about 4-fold, prolonged mean resident time (MRT) by more than 8-fold and reduced the elimination rate constant by greater than 68-fold. In conclusion, the present nanocarriers with high drug-loading capacity represent an efficient tumor-targeting drug delivery system with promising potential for cancer therapy.
传统纳米颗粒存在快速血液清除和早期爆发释放的固有缺陷，导致肿瘤选择性差。iRGD 肽被广泛认为是一种有效的细胞膜穿透肽，靶向 αVβ3 整合素。本文制备了载药量大的紫杉醇（PTX）核壳纳米胶囊（NCs）和 iRGD 修饰的 NCs（iRGD-NCs），以增强疏水性差的化疗药物的抗肿瘤活性。NCs 和 iRGD-NCs 表现出增强的体外和体内肿瘤靶向和穿透性；后者表现出更好的抗肿瘤活性，因为 iRGD 增强了 NCs 在肿瘤中的积累和穿透。NCs 具有细胞相容性、组织相容性，对其他健康组织无毒。NCs 的内吞作用通过脂质筏以能量依赖的方式介导，导致 PTX 对癌细胞的细胞毒性更好。与商业产品相比，载紫杉醇的 NCs（PTX-NCs）使 AUC 增加了约 4 倍，MRT 延长了 8 倍以上，消除率常数降低了 68 倍以上。总之，具有高载药能力的新型载体代表了一种有效的肿瘤靶向药物传递系统，具有癌症治疗的广阔前景。
