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载有多柔比星的聚（ε-己内酯）-b-聚（N-乙烯基吡咯烷酮）胶束的靶向递送增强了淋巴瘤的抗肿瘤效果。

Targeted delivery of doxorubicin-loaded poly (ε-caprolactone)-b-poly (N-vinylpyrrolidone) micelles enhances antitumor effect in lymphoma.

作者信息

Hira Sumit Kumar, Mishra Avnish Kumar, Ray Biswajit, Manna Partha Pratim

机构信息

Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, India.

Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi, India.

出版信息

PLoS One. 2014 Apr 8;9(4):e94309. doi: 10.1371/journal.pone.0094309. eCollection 2014.

DOI:10.1371/journal.pone.0094309
PMID:24714166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3979807/
Abstract

BACKGROUND

The present study was motivated by the need to design a safe nano-carrier for the delivery of doxorubicin which could be tolerant to normal cells. PCL63-b-PNVP90 was loaded with doxorubicin (6 mg/ml), and with 49.8% drug loading efficiency; it offers a unique platform providing selective immune responses against lymphoma.

METHODS

In this study, we have used micelles of amphiphilic PCL63-b-PNVP90 block copolymer as nano-carrier for controlled release of doxorubicin (DOX). DOX is physically entrapped and stabilized in the hydrophobic cores of the micelles and biological roles of these micelles were evaluated in lymphoma.

RESULTS

DOX loaded PCL63-b-PNVP90 block copolymer micelles (DOX-PCL63-b-PNVP90) shows enhanced growth inhibition and cytotoxicity against human (K-562, JE6.1 and Raji) and mice lymphoma cells (Dalton's lymphoma, DL). DOX-PCL63-b-PNVP90 demonstrates higher levels of tumoricidal effect against DOX-resistant tumor cells compared to free DOX. DOX-PCL63-b-PNVP90 demonstrated effective drug loading and a pH-responsive drug release character besides exhibiting sustained drug release performance in in-vitro and intracellular drug release experiments.

CONCLUSION

Unlike free DOX, DOX-PCL63-b-PNVP90 does not show cytotoxicity against normal cells. DOX-PCL63-b-PNVP90 prolonged the survival of tumor (DL) bearing mice by enhancing the apoptosis of the tumor cells in targeted organs like liver and spleen.

摘要

背景

本研究旨在设计一种安全的纳米载体用于递送阿霉素，该载体对正常细胞具有耐受性。聚己内酯63-嵌段-聚N-乙烯基吡咯烷酮90（PCL63-b-PNVP90）负载阿霉素（6毫克/毫升），载药效率为49.8%；它提供了一个独特的平台，可引发针对淋巴瘤的选择性免疫反应。

方法

在本研究中，我们使用两亲性PCL63-b-PNVP90嵌段共聚物胶束作为纳米载体来控制阿霉素（DOX）的释放。DOX通过物理方式包封并稳定在胶束的疏水核心中，并在淋巴瘤中评估了这些胶束的生物学作用。

结果

负载DOX的PCL63-b-PNVP90嵌段共聚物胶束（DOX-PCL63-b-PNVP90）对人（K-562、JE6.1和Raji）和小鼠淋巴瘤细胞（道尔顿淋巴瘤，DL）显示出增强的生长抑制和细胞毒性。与游离DOX相比，DOX-PCL63-b-PNVP90对DOX耐药肿瘤细胞表现出更高水平的杀肿瘤作用。在体外和细胞内药物释放实验中，DOX-PCL63-b-PNVP90除了表现出持续的药物释放性能外，还展示了有效的载药能力和pH响应性药物释放特性。

结论

与游离DOX不同，DOX-PCL63-b-PNVP90对正常细胞没有细胞毒性。DOX-PCL63-b-PNVP90通过增强肝脏和脾脏等靶器官中肿瘤细胞的凋亡，延长了荷瘤（DL）小鼠的生存期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/1bd9d2058646/pone.0094309.g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/e0eb4b702e70/pone.0094309.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/613fd3c0c119/pone.0094309.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/d780e2955320/pone.0094309.g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/b6d37f8b9aa6/pone.0094309.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/85c10e76d3bb/pone.0094309.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf8/3979807/ed62da83f0ab/pone.0094309.g009.jpg
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