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载二棕榈酰磷脂酰胆碱的还原敏感聚合物囊用于递送 DM1 至 HER-2 阳性乳腺癌。

Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer.

机构信息

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, Berlin 14195, Germany.

Institute of Active Polymers, Helmholtz-Zentrum HEREON, Teltow 14513, Germany.

出版信息

Biomacromolecules. 2024 Jul 8;25(7):4440-4448. doi: 10.1021/acs.biomac.4c00512. Epub 2024 Jun 22.

DOI:10.1021/acs.biomac.4c00512
PMID:38907698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11238329/
Abstract

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment.

摘要

具有延长循环时间、潜在的多样化功能化以及较少毒素相关限制的超分子递药系统已被广泛研究。在本研究中，我们构建了一种线性聚甘油壳聚合物囊，连接有抗 HER-2 抗体曲妥珠单抗。然后，我们通过动态二硫键将抗癌药物 DM1 共价加载到聚合物囊中。所得的曲妥珠单抗-聚合物囊-DM1（Tra-PS-DM1）的平均粒径为 95.3nm，载药效率高达 99.3%。除了具有优越的稳定性外，我们还观察到在还原条件下可以快速、可控地释放 DM1。与天然聚合物囊相比，Tra-PS-DM1 显示出显著提高的细胞摄取能力和显著降低的 IC50，在 HER-2 阳性癌细胞中降低了 17 倍。此外，Tra-PS-DM1 对 HER-2 阳性肿瘤球状体表现出优异的生长抑制作用；具体而言，BT474 肿瘤球在 12 小时治疗后缩小了 62%。具有出色稳定性和靶向性的 PG 壳 Tra-PS-DM1 似乎是治疗 HER-2 阳性肿瘤的一种有吸引力的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/cd03c780b19e/bm4c00512_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/7fe8b6b45780/bm4c00512_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/2fc5745b6e47/bm4c00512_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/ebf5549a0ce0/bm4c00512_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/859a7871ea35/bm4c00512_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/faffc42b7b1a/bm4c00512_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/94e68595809d/bm4c00512_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/cd03c780b19e/bm4c00512_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/7fe8b6b45780/bm4c00512_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/2fc5745b6e47/bm4c00512_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/ebf5549a0ce0/bm4c00512_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/859a7871ea35/bm4c00512_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/faffc42b7b1a/bm4c00512_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/94e68595809d/bm4c00512_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/11238329/cd03c780b19e/bm4c00512_0006.jpg

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