Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)-poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy
Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)-poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy
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DOI：
10.1097/cad.0000000000000631
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发表时间：
2018-08-01
影响因子：
2.3
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
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作者：
Dong, Shiliang;Guo, Yuexin;Zhang, Mingzhi
传统化疗药物在抗肿瘤治疗中的临床疗效有限。多药联合及辅助药物载体的应用是克服局限性，同时又能最大限度地减少单药剂量，获得肿瘤治疗协同效应的可行策略。然而，全身毒性、耐药、肿瘤复发仍是不可避免的。在这里，我们开发了核壳纳米颗粒（NPs）来封装紫杉醇（PTX）和吉西他滨（GEM）用于乳腺癌治疗。我们发现NPs可以封装PTX和GEM，封装效率分别为96.3和95.13%。这些NPs的载药量分别为2.71% （PTX）和2.64% （GEM）。值得注意的是，在相同浓度下，与单独使用PTX或单独使用GEM相比，GEM和PTX联合使用的抗癌效果更强，这表明GEM和PTX具有协同作用。此外，与游离药物相比，甲氧基聚乙二醇-聚丙交酯-乙醇酸酯包封PTX和GEM也显示出增强的抗癌作用（81.5%的肿瘤抑制）和降低的体内全身毒性（65%的肿瘤抑制）。综上所述，甲氧基聚乙二醇-聚丙交酯-乙醇酸酯联合给药PTX和GEM可能在乳腺癌治疗的临床应用中具有重要的潜力。
Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core-shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy.