Thermal and pH Sensitive Multifunctional Polymer Nanoparticles for Cancer Imaging and Therapy.

Thermal and pH Sensitive Multifunctional Polymer Nanoparticles for Cancer Imaging and Therapy.
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DOI:
10.1039/c4ra01112k
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发表时间:
2014-01-01
期刊:
影响因子:
3.9
通讯作者:
McGoron AJ
McGoron AJ
中科院分区:
化学3区
文献类型:
--
作者:
Lei T;Manchanda R;Fernandez-Fernandez A;Huang YC;Wright D;McGoron AJ

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在这项研究中,我们制备了新型聚苹果酸甘油共十二烷二酸酯(PGMD) NPs,其中含有一种显像/热疗剂(IR820)和一种化疗剂(阿霉素,DOX)。采用热缩聚法制备PGMD聚合物。采用单油乳化技术制备了负载IR820和DOX的PGMD NPs。所测NPs的尺寸约为150 nm。DOX和IR820的载药效率分别为4%和8%左右。与pH=7.4相比,酸性环境(pH=5.0)诱导了更高的DOX释放。将温度升高至42°C,激光照射也能促进DOX释放。载药NPs在MES-SA细胞中的细胞毒性相当,但在Dx5细胞中的细胞毒性高于游离药物(p<0.05)。热疗联合化疗可改善两种细胞系的细胞毒性。NP制剂可显著提高小鼠尾静脉注射后IR820的血浆半衰期。
In this study, we prepared novel poly(Glycerol malate co-dodecanedioate) (PGMD) NPs containing an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The PGMD polymer was prepared by thermal condensation. IR820 and DOX loaded PGMD NPs were prepared using the single oil emulsion technique. The size of the NPs measured was around 150 nm. Drug loading efficiency of DOX and IR820 was around 4% and 8%, respectively. An acidic environment (pH=5.0) induced higher DOX release as compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of the drug loaded NPs was comparable in MES-SA but was higher in Dx5 cells compared to free drug (p<0.05). The combination of hyperthermia and chemotherapy improved cytotoxicity in both cell lines. The NP formulation significantly improved the plasma half-life of IR820 in mice after tail vein injection.