Enhanced 4T1 Breast Carcinoma Anticancer Activity by Co-Delivery of Doxorubicin and Curcumin with Core-Shell Drug-Carrier Based on Heparin Modified Poly(L-lactide) Grafted Polyethylenimine Cationic Nanoparticles
Enhanced 4T1 Breast Carcinoma Anticancer Activity by Co-Delivery of Doxorubicin and Curcumin with Core-Shell Drug-Carrier Based on Heparin Modified Poly(L-lactide) Grafted Polyethylenimine Cationic Nanoparticles
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基于肝素修饰聚L-丙交酯接枝聚乙烯亚胺阳离子纳米粒的核壳药物载体共同递送阿霉素和姜黄素增强4T1乳腺癌抗癌活性
DOI：
10.1166/jbn.2014.1785
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发表时间：
2014-02-01
影响因子：
2.9
通讯作者：
Qian, Zhiyong
中科院分区：
文献类型：
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作者：
Guo, Qingfa;Li, Xiaolu;Qian, Zhiyong
单一化疗药物在抗肿瘤治疗中表现出一定的局限性，如耐药性的产生、严重的不良反应和治疗方案的限制。两种或多种治疗药物的组合是克服这些局限性的可行策略。本文报道了以姜黄素（Cur）为核的疏水聚乳酸（PLLA）和以肝素为壳的亲水阿霉素（DOX）的核壳纳米粒（NPs）的共递送研究。通过透射电子显微镜（TEM）和马尔文Zetasizer研究了Cur-PEA NPs、Cur-PEA/肝素NPs和吸附到Cur-PEA/肝素NPs（DOX-Cur NPs）中的DOX的表征。对DOX-Cur NP的细胞摄取的研究表明，两种药物都被4 T1肿瘤细胞有效摄取。此外，如通过流式细胞术（FCM）测量的，在相同浓度下，DOX-Cur NP比单独的DOX或Cur更有效地抑制4 T1肿瘤细胞生长。我们发现静脉内注射DOX-Cur NPs有效地抑制了体内皮下4 T1乳腺癌的生长（p < 0.01），并延长了经治疗的4 T1乳腺癌小鼠的存活。此外，在用DOX-Cur NP处理的小鼠中对心脏组织的病理损伤比用游离DOX处理的小鼠显著更轻。本研究表明，DOX-Cur纳米粒可能在乳腺癌治疗中有很好的应用前景。
Use of single chemotherapy agents has shown some limitations in anti-tumor treatment, such as development of drug resistance, severe adverse reactions and limited regime for therapeutic use. Combination of two or more therapeutic drugs is a feasible strategy to overcome these limitations. This paper reports study of co-delivery by core-shell nanoparticles (NPs) with hydrophobic PLLA core loaded with curcumin (Cur) and hydrophilic heparin shell adsorbing Doxorubicin (DOX). Characterizations of Cur-PEA NPs, Cur-PEA/heparin NPs and DOX adsorbing into Cur-PEA/heparin NPs (DOX-Cur NPs) were also investigated by transmission electron microscope (TEM) and Malvern Zetasizer. Studies on cellular uptake of DOX-Cur NPs demonstrated that both drugs were effectively taken up by 4T1 tumor cells. Furthermore, DOX-Cur NPs suppressed 4T1 tumor cells growth more efficiently than either DOX or Cur alone at the same concentrations, as measured by flow cytometry (FCM). We found out that intravenous injection of DOX-Cur NPs efficiently inhibited growth of subcutaneous 4T1 breast carcinoma in vivo (p < 0.01) and prolonged survival of the treated 4T1 breast carcinoma mice. Moreover, the pathological damage to the cardiac tissue in mice treated with DOX-Cur NPs was significantly less severe than that of mice treated with free DOX. This study suggested that DOX-Cur NPs may have promising applications in breast carcinoma therapy.