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首页> 外文期刊>Nanotechnology >Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles
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Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

机译：基于自组装多功能聚合物纳米粒子的阿霉素，全反式维甲酸和低分子量肝素联合化疗

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Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects.
机译：基于阿霉素（DOX），全反式维甲酸（ATRA）和低分子量肝素（LMWH）的互补作用，DOX，ATRA和LMWH的联合治疗有望发挥增强的抗肿瘤作用并降低副作用。在这项研究中，两亲LMWH-ATRA缀合物被合成用于封装DOX。这样，通过化学和物理两种方式将DOX，ATRA和LMWH组装到一个纳米系统中，从而获得了一种新型的抗肿瘤靶向药物递送系统，该系统可以实现将具有不同特性的多种药物同时递送至肿瘤。 LMWH-ATRA纳米颗粒对DOX表现出良好的负载能力，具有优异的理化性质，良好的生物相容性以及良好的分化诱导活性和抗血管生成活性。载药量高达18.7％，包封率为78.8％。还发现载有DOX的LMWH-ATRA纳米颗粒（DHR纳米颗粒）可以通过内吞途径被肿瘤细胞有效吸收，并首先主要分布在细胞质中，然后转移到细胞核中。细胞活力测定表明，DHR纳米颗粒可维持DOX对MCF-7细胞的细胞毒性作用。此外，体内成像分析表明，与游离DiR相比，负载DiR的LMWH-ATRA纳米颗粒可以更有效地靶向肿瘤。此外，与游离药物溶液相比，DHR纳米粒子具有更高的抗癌活性并减少了副作用。这些结果表明，DHR纳米颗粒可被视为具有较低不良反应的联合癌症化疗的有希望的靶向递送系统。

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