Self-targeted, bacillus-shaped, and controlled-release methotrexate prodrug polymeric nanoparticles for intratumoral administration with improved therapeutic efficacy in tumor-bearing mice
Self-targeted, bacillus-shaped, and controlled-release methotrexate prodrug polymeric nanoparticles for intratumoral administration with improved therapeutic efficacy in tumor-bearing mice
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自靶向、芽孢杆菌状、控释甲氨蝶呤前药聚合物纳米颗粒，用于肿瘤内给药，可提高荷瘤小鼠的治疗效果
DOI：
10.1039/c5tb00724k
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发表时间：
2015-01-01
影响因子：
7
通讯作者：
Lin, Changjian
中科院分区：
文献类型：
--
作者：
Lin, Jinyan;Li, Yanxiu;Lin, Changjian
肿瘤细胞内环境中药物分布不均匀、药物浓度低，仍然限制了肿瘤化疗药物的治疗效果。局部给药（物理靶向）结合受体介导的给药（化学靶向）和新的形状设计辅助是治疗浸润性肿瘤（即使是那些术后持续存在的肿瘤）的一种很有前途的策略。在本文中，我们通过自组装技术结合挤压SPG膜制备了染料和甲氨蝶呤（MTX）功能化的纳米杆菌（MPEG-PLA-MTX-Cy5.5 NB）用于肿瘤内给药，其中杆菌状的MPEG-PLA-MTX-Cy5.5 NB具有双作用MTX，可以特异性和有效地增强其细胞摄取，同时避免其从肿瘤部位分散。在瘤内给药H-22异种移植小鼠模型后，与MPEG-PLA-Cy5.5纳米球（MPEG-PLA-Cy5.5 NSs）和MPEG-PLA-MTX-Cy5.5纳米球（MPEG-PLA-MTX-Cy5.5 NSs）相比，MPEG-PLA-MTX-Cy5.5纳米球（MPEG-PLA-MTX-Cy5.5 NSs）更有效地将药物递送到肿瘤。与游离MTX和MPEG-PLA-MTX-Cy5.5 NSs相比，控释的MPEG-PLA-MTX-Cy5.5 NB也能显著抑制肿瘤生长，提高治疗效果。这些平台是高度聚合、灵活和简化的系统，可以作为纳米颗粒进一步设计的指导，具有革命性的新形状和功能，用于临床应用。
Poor drug distribution and inefficient drug concentrations within the tumor intracellular environment still limit the therapeutic efficacy of drugs for cancer chemotherapy. Local drug delivery (physical targeting) combined with receptor-mediated drug delivery (chemical targeting) and assistance by a novel shape design is a promising strategy to treat the infiltrating tumor (even those that persist post surgery). In this paper, we prepared dye and methotrexate (MTX) functionalized nanobacilli (MPEG-PLA-MTX-Cy5.5 NB) by a self-assembly technique combined with extrusion through a SPG membrane for intratumoral administration, in which the bacillus-shaped MPEG-PLA-MTX-Cy5.5 NB were armed with a dual-acting MTX that can specifically and efficiently enhance their cellular uptake, while avoiding their dispersion from tumor sites. After intratumoral administration to a H-22 xenograft mouse model, the MPEG-PLA-MTX-Cy5.5 NB delivered the drug more effectively to the tumor compared to the MPEG-PLA-Cy5.5 nanospheres (MPEG-PLA-Cy5.5 NSs) and MPEG-PLA-MTX-Cy5.5 nanospheres (MPEG-PLA-MTX-Cy5.5 NSs). Compared to the free MTX and MPEG-PLA-MTX-Cy5.5 NSs, the controlled-release MPEG-PLA-MTX-Cy5.5 NB also significantly inhibited the tumor growth and improved therapeutic efficacy. The platforms are highly convergent, flexible and simplified systems that may serve as guides in the further design of nanoparticles with a revolutionary new shape and function for clinical applications.