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由可生物降解的树枝状共聚物聚谷氨酸 - D-α-生育酚聚乙二醇1000琥珀酸酯自组装而成的载DACHPt纳米颗粒用于多药耐药肺癌治疗。

DACHPt-Loaded Nanoparticles Self-assembled from Biodegradable Dendritic Copolymer Polyglutamic Acid--D-α-Tocopheryl Polyethylene Glycol 1000 Succinate for Multidrug Resistant Lung Cancer Therapy.

作者信息

Tsai Hsiang-I, Jiang Lijuan, Zeng Xiaowei, Chen Hongbo, Li Zihuang, Cheng Wei, Zhang Jinxie, Pan Jie, Wan Dong, Gao Li, Xie Zhenhua, Huang Laiqiang, Mei Lin, Liu Gan

机构信息

School of Life Sciences, Tsinghua University, Beijing, China.

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China.

出版信息

Front Pharmacol. 2018 Feb 21;9:119. doi: 10.3389/fphar.2018.00119. eCollection 2018.

DOI:10.3389/fphar.2018.00119
PMID:29515445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5826327/
Abstract

The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid--D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu--TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.

摘要

铂类抗肿瘤药物的临床应用仍然在很大程度上受到严重副作用以及多药耐药性（MDR）的限制。为了解决这些问题，我们通过聚（酰胺胺）-聚谷氨酸-D-α-生育酚聚乙二醇1000琥珀酸酯（PAM-PGlu-TPGS）和二氯二氨环己烷铂（II）（DACHPt）的自组装制备了负载DACHPt的纳米颗粒（NP-TPGS-Pt）。NP-TPGS-Pt表现出强大的稳定性和类似于含聚乙二醇纳米颗粒（NP-PEG-Pt）的pH响应性DACHPt释放曲线。同时，与NP-PEG-Pt相比，NP-TPGS-Pt在耐铂的A549/DDP人肺癌细胞中表现出高效的基于纳米颗粒的细胞摄取，并且比游离奥沙利铂和NP-PEG-Pt具有更强的细胞毒性。最后，证明这种NP-TPGS-Pt对耐铂肿瘤生长具有出色的抑制作用，远优于游离奥沙利铂和NP-PEG-Pt。因此，这种NP-TPGS-Pt为对抗多药耐药癌症提供了一种新型的强大纳米药物平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/f27fe601dd20/fphar-09-00119-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/84f2b9e359d5/fphar-09-00119-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/0adc7bb0aaeb/fphar-09-00119-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/1e863cc17a86/fphar-09-00119-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/ecc498496d93/fphar-09-00119-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/c5d16edb61d2/fphar-09-00119-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/3cd1a78b5d80/fphar-09-00119-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/bc1306ba8c9d/fphar-09-00119-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/f27fe601dd20/fphar-09-00119-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/84f2b9e359d5/fphar-09-00119-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/0adc7bb0aaeb/fphar-09-00119-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/1e863cc17a86/fphar-09-00119-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/ecc498496d93/fphar-09-00119-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/c5d16edb61d2/fphar-09-00119-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/3cd1a78b5d80/fphar-09-00119-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/bc1306ba8c9d/fphar-09-00119-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3470/5826327/f27fe601dd20/fphar-09-00119-g0008.jpg

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