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负载紫杉醇和依托泊苷的聚合物纳米颗粒用于有效联合治疗人类骨肉瘤

Paclitaxel and etoposide co-loaded polymeric nanoparticles for the effective combination therapy against human osteosarcoma.

作者信息

Wang Bing, Yu Xiu-Chun, Xu Song-Feng, Xu Ming

机构信息

Department of Orthopeadic, The General Hospital of Jinan Military Commanding Region, No. 25 Shifan Road, Tianqiao District, Jinan, Shandong, 250031, China.

出版信息

J Nanobiotechnology. 2015 Mar 21;13:22. doi: 10.1186/s12951-015-0086-4.

DOI:10.1186/s12951-015-0086-4
PMID:25880868
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4377179/
Abstract

BACKGROUND

The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.

RESULTS

The resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.

CONCLUSION

Taken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.

摘要

背景

将具有不同药理作用的化疗药物联合使用已成为一种有前景的癌症治疗策略。本研究考察了负载紫杉醇(PTX)和依托泊苷(ETP)的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒治疗骨肉瘤的抗肿瘤潜力。

结果

所得载药PLGA纳米粒呈现纳米尺寸,形态为均匀的球形。在整个研究期间,纳米粒对PTX和ETP均呈现缓释特性,无任何初始突释迹象。与单独使用天然药物或混合药物相比,载药PLGA纳米粒组合增强了对MG63和Saos-2骨肉瘤细胞系的细胞毒性作用。此外,纳米粒在MG63细胞中呈现出明显的基于时间的摄取。抗癌药物的共递送导致细胞周期阻滞和细胞凋亡增强。结果清楚地表明,联合用药显著提高了化疗药物的治疗指数。纳米粒组合的更大抑制作用在全身癌症治疗中将具有很大优势。

结论

综上所述,我们的研究表明基于PTX-ETP/PLGA纳米粒的联合疗法在治疗骨肉瘤方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/76763e3e5996/12951_2015_86_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/0fe5c1672a66/12951_2015_86_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/d5a2378a6ab9/12951_2015_86_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/f75d46857942/12951_2015_86_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/88dd7062db24/12951_2015_86_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/74a02424d9c9/12951_2015_86_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/3bc8309dd82f/12951_2015_86_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/76763e3e5996/12951_2015_86_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/0fe5c1672a66/12951_2015_86_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/d5a2378a6ab9/12951_2015_86_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/f75d46857942/12951_2015_86_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/88dd7062db24/12951_2015_86_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/74a02424d9c9/12951_2015_86_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/3bc8309dd82f/12951_2015_86_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4817/4377179/76763e3e5996/12951_2015_86_Fig7_HTML.jpg

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