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载药纳米粒阿霉素抑制免疫缺陷荷瘤鼠原位卵巢移植瘤生长的实验研究。

Nanoparticle-Encapsulated Epirubicin Efficacy in the Inhibition of Growth of Orthotopic Ovarian Patient-Derived Xenograft in Immunocompromised Mice.

机构信息

NanoVelos S.A., Rakowiecka 36, 02-532 Warsaw, Poland.

NanoGroup S.A., Rakowiecka 36, 02-532 Warsaw, Poland.

出版信息

Int J Mol Sci. 2024 Jan 4;25(1):645. doi: 10.3390/ijms25010645.


DOI:10.3390/ijms25010645
PMID:38203818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10779551/
Abstract

Epirubicin hydrochloride (EPI) is an anticancer drug widely used in the treatment of many solid tumors, including ovarian cancer. Because of its anatomical location, ovarian cancer shows symptoms when it is already in an advanced stage and is thus more difficult to treat. Epirubicin hydrochloride kills cancer cells effectively, but its dose escalation is limited by its severe toxicity. By encapsulating epirubicin in dextran-based nanoparticles (POLEPI), we expected to deliver higher and thus clinically more effective doses directly to tumors, where epirubicin would be released and retained longer in the tumor. The antitumor activity of POLEPI compared to EPI was first tested ex vivo in a series of ovarian cancer patient-derived tumor xenografts (PDX). The most promising PDX was then implanted orthotopically into immunocompromised mice, and tumor growth was monitored via magnetic resonance imaging (MRI). Although we succeeded in suppressing the growth of ovarian cancer derived from a patient, in a mouse model by 70% compared to 40% via EPI in 5 days after only one injection, we could not eliminate serious side effects, and the study was terminated prematurely for humane reasons.

摘要

盐酸表柔比星(EPI)是一种广泛用于治疗多种实体瘤的抗癌药物,包括卵巢癌。由于其解剖位置,卵巢癌在晚期才出现症状,因此更难治疗。盐酸表柔比星可有效杀死癌细胞,但由于其严重的毒性,其剂量的增加受到限制。通过将表柔比星包封在基于葡聚糖的纳米粒子(POLEPI)中,我们期望将更高、更有效的剂量直接递送到肿瘤部位,在那里表柔比星将在肿瘤中更长时间地释放和保留。我们首先在一系列卵巢癌患者来源的肿瘤异种移植(PDX)中体外测试了 POLEPI 与 EPI 的抗肿瘤活性。最有前途的 PDX 然后被原位植入免疫功能低下的小鼠中,并通过磁共振成像(MRI)监测肿瘤生长。尽管我们成功地抑制了来自患者的卵巢癌细胞的生长,与 EPI 相比,在仅注射一次后的 5 天内,小鼠模型中的抑制率为 70%,而不是 40%,但我们无法消除严重的副作用,出于人道原因,研究提前终止。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/c5ba93f777da/ijms-25-00645-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/3e6fb0a0ef7f/ijms-25-00645-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/3b43b93bb167/ijms-25-00645-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/c12411382ccd/ijms-25-00645-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/7559245baf22/ijms-25-00645-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/702cec56a121/ijms-25-00645-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/1b95c67fe909/ijms-25-00645-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/eeb6ba64684e/ijms-25-00645-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/c5ba93f777da/ijms-25-00645-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/3e6fb0a0ef7f/ijms-25-00645-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/3b43b93bb167/ijms-25-00645-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/c12411382ccd/ijms-25-00645-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/7559245baf22/ijms-25-00645-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/702cec56a121/ijms-25-00645-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/1b95c67fe909/ijms-25-00645-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/eeb6ba64684e/ijms-25-00645-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc20/10779551/c5ba93f777da/ijms-25-00645-g008.jpg

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Nanoparticle-Encapsulated Epirubicin Efficacy in the Inhibition of Growth of Orthotopic Ovarian Patient-Derived Xenograft in Immunocompromised Mice.

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[3]
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[4]
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[6]
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引用本文的文献

[1]
Biodistribution of Polyaldehydedextran Nanoparticle-Encapsulated Epirubicin in Ovarian Tumor-Bearing Mice via Optical Imaging.

Int J Mol Sci. 2025-1-24

本文引用的文献

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Pharmaceutics. 2023-6-26

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CA Cancer J Clin. 2021-5

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