Ratiometric co-encapsulation and co-delivery of doxorubicin and paclitaxel by tumor-targeted lipodisks for combination therapy of breast cancer
Ratiometric co-encapsulation and co-delivery of doxorubicin and paclitaxel by tumor-targeted lipodisks for combination therapy of breast cancer
复制标题
通过肿瘤靶向脂质盘按比例共封装和共同递送阿霉素和紫杉醇用于乳腺癌的联合治疗
DOI：
10.1016/j.ijpharm.2019.02.009
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发表时间：
2019-04-05
影响因子：
5.8
通讯作者：
Xu, Ximing
中科院分区：
文献类型：
--
作者：
Feng, Chunlai;Zhang, Haisheng;Xu, Ximing
联合疗法对于某些晚期耐药癌症是一种很有希望的治疗方法。虽然体外有效抑制多种肿瘤细胞的报道，但由于不受控制的比例递送，联合治疗需要在体内改善。在这项研究中，研究人员开发了一种肿瘤靶向脂盘纳米颗粒制剂，用于在一个单一平台上比例加载和运输两种疏水模型药物，阿霉素（DOX）和紫杉醇（PTX）。此外，微酸性ph敏感肽（SAPSP）结合到脂碟中，有效地增强了肿瘤靶向和细胞内化。所得的载胶脂片直径约为30 nm，具有ph敏感性。两种药物通过脂碟的比例共递送在耐药的MCF-7/ADR细胞系及其亲本MCF-7细胞系的体外实验中得到证实，并在体内荷瘤小鼠模型中与游离药物的鸡尾酒溶液进行了比较。共载脂盘对培养的肿瘤细胞具有更好的细胞毒性，特别是对具有协同药物比的耐药肿瘤细胞。在体内异种移植小鼠模型中，共载脂盘的抗肿瘤能力通过对MCF-7或MCF-7/ADR肿瘤的显著抑制作用得到了证明，这可能归因于两种药物在肿瘤组织中的增加和比例积累。因此，肿瘤特异性脂盘对于DOX和PTX联合治疗完全发挥协同抗癌作用至关重要。因此，对于共载脂盘，体外细胞毒性数据可用于预测其体内抑制活性，有可能提高协同治疗的临床效果。
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) in-corporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained coloaded lipodisks were approximately 30 nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro, as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo, potentially enhancing the clinical outcome of synergistic therapy.