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聚乙二醇化顺铂纳米颗粒以响应 pH 的方式治疗结直肠癌。

PEGylated Cisplatin Nanoparticles for Treating Colorectal Cancer in a pH-Responsive Manner.

机构信息

Department of General Surgery, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, 050000 Hebei, China.

Department of Pharmacy, Hebei University of Science and Technology, Yuxiang Street 26, Shijiazhuang, Hebei 050018, China.

出版信息

J Immunol Res. 2022 Aug 5;2022:8023915. doi: 10.1155/2022/8023915. eCollection 2022.

DOI:10.1155/2022/8023915
PMID:36033392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9410866/
Abstract

Colorectal cancer (CRC) is a common malignant tumor, and its incidence ranks third and mortality rate ranks second in the world. Cisplatin cannot target CRC cells and has notable toxicity, which significantly limits its clinical application. The emerging PEGylated nanodrug delivery system can improve circulation time and enhance tumor targeting. In this study, the HA-mPEG-Cis NPs were synthesized by self-assembly, which can target CD44-positive CRC cells and dissolve the PEG hydration layer responsive to the weakly acidic tumor environment. The average hydrodynamic diameter of HA-mPEG-Cis NPs was 48 nm with the polydispersity index of 0.13. The cisplatin release was in a pH-responsive manner. The HA-mPEG-Cis NPs group showed the highest apoptosis rate (25.1%). The HA-mPEG-Cis NPs exhibited antitumor efficacy via the PI3K/AKT/mTOR signaling pathway. The HA-mPEG-Cis NPs showed the lowest tumor volume and weight among all the groups in CT26 cell-bearing mouse model. The HA-mPEG-Cis nanodrug delivery system not only increases the stability and circulation time but also reduces the side effects of loaded cisplatin. Overall, the and experiments confirmed the satisfied antitumor efficacy of HA-mPEG-Cis NPs. Therefore, this study provides a rational design for application of pH-responsive HA-mPEG-Cis nanodrug delivery system in the future.

摘要

结直肠癌（CRC）是一种常见的恶性肿瘤，其发病率居世界第三，死亡率居世界第二。顺铂不能靶向 CRC 细胞，且具有显著的毒性，这极大地限制了其临床应用。新兴的 PEG 化纳米药物递送系统可以提高循环时间并增强肿瘤靶向性。本研究通过自组装合成了 HA-mPEG-Cis NPs，其可以靶向 CD44 阳性 CRC 细胞，并溶解对弱酸性肿瘤环境有响应的 PEG 水化层。HA-mPEG-Cis NPs 的平均水动力学直径为 48nm，多分散指数为 0.13。顺铂的释放呈 pH 响应性。HA-mPEG-Cis NPs 组表现出最高的凋亡率（25.1%）。HA-mPEG-Cis NPs 通过 PI3K/AKT/mTOR 信号通路发挥抗肿瘤作用。在 CT26 荷瘤小鼠模型中，HA-mPEG-Cis NPs 组的肿瘤体积和重量均为最低。HA-mPEG-Cis 纳米药物递送系统不仅提高了稳定性和循环时间，还降低了载药顺铂的副作用。总之，体内外实验均证实了 HA-mPEG-Cis NPs 具有令人满意的抗肿瘤疗效。因此，本研究为 pH 响应性 HA-mPEG-Cis 纳米药物递送系统的未来应用提供了合理的设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/d19fdb1e8835/JIR2022-8023915.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/f245461ab1f2/JIR2022-8023915.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/5a774ec53b50/JIR2022-8023915.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/be2997a0537b/JIR2022-8023915.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/ccdccd2372ef/JIR2022-8023915.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/734d9d9fc8c2/JIR2022-8023915.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/d19fdb1e8835/JIR2022-8023915.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/f245461ab1f2/JIR2022-8023915.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/5a774ec53b50/JIR2022-8023915.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/be2997a0537b/JIR2022-8023915.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/114c020bf88c/JIR2022-8023915.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/ccdccd2372ef/JIR2022-8023915.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/734d9d9fc8c2/JIR2022-8023915.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788c/9410866/d19fdb1e8835/JIR2022-8023915.007.jpg

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