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聚唾液酸功能化脂质体高效递送和厚朴酚抑制乳腺癌生长和转移

Polysialic acid-functionalized liposomes for efficient honokiol delivery to inhibit breast cancer growth and metastasis.

机构信息

Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, P.R. China.

College of Pharmacy, Qiqihar Medical University, Qiqihar, P.R. China.

出版信息

Drug Deliv. 2023 Dec;30(1):2181746. doi: 10.1080/10717544.2023.2181746.

DOI:10.1080/10717544.2023.2181746
PMID:36803115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9946320/
Abstract

To improve the anti-metastasis effects of honokiol (HNK) on breast cancer, we designed cationic liposomes (Lip) in which HNK was encapsulated into Lip, and its surface was modified with negatively charged polysialic acid (PSA-Lip-HNK) for efficient treatment of breast cancer. PSA-Lip-HNK possessed a homogeneous spherical shape and high encapsulation efficiency. 4T1 cell experiments indicated that PSA-Lip-HNK increased cellular uptake and cytotoxicity via the endocytosis pathway mediated by PSA and selectin receptors. Furthermore, the significant antitumor metastasis impact of PSA-Lip-HNK was confirmed by wound healing and cell migration and invasion. Enhanced tumor accumulation of the PSA-Lip-HNK was observed in 4T1 tumor-bearing mice by living fluorescence imaging. For antitumor experiments using 4T1 tumor-bearing mice, PSA-Lip-HNK exhibited a higher tumor growth and metastasis inhibition compared with unmodified liposomes. Therefore, we believe that PSA-Lip-HNK well combined biocompatible PSA nano-delivery and chemotherapy, providing a promising drug delivery approach for metastatic breast cancer therapy.

摘要

为了提高霍诺醇（HNK）对乳腺癌的抗转移作用，我们设计了阳离子脂质体（Lip），将 HNK 包裹在 Lip 中，并对其表面进行负电荷化的多糖唾液酸（PSA）修饰，以实现高效治疗乳腺癌。PSA-Lip-HNK 具有均匀的球形形状和高包封效率。4T1 细胞实验表明，PSA-Lip-HNK 通过 PSA 和选择素受体介导的内吞途径增加细胞摄取和细胞毒性。此外，通过划痕愈合、细胞迁移和侵袭实验证实了 PSA-Lip-HNK 对肿瘤转移的显著抑制作用。通过活体荧光成像观察到，PSA-Lip-HNK 在 4T1 荷瘤小鼠中的肿瘤积累增强。在使用 4T1 荷瘤小鼠的抗肿瘤实验中，PSA-Lip-HNK 表现出比未修饰脂质体更高的肿瘤生长和转移抑制作用。因此，我们认为 PSA-Lip-HNK 很好地结合了生物相容性 PSA 纳米递药和化疗，为转移性乳腺癌治疗提供了一种有前途的药物递送方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/13c0681b2510/IDRD_A_2181746_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/31b8b2b22599/IDRD_A_2181746_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/9f1da43bddd0/IDRD_A_2181746_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/ade10cfdc779/IDRD_A_2181746_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/ff3ed696ca41/IDRD_A_2181746_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/700262c87e18/IDRD_A_2181746_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/1bdd5d03ce21/IDRD_A_2181746_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/d69faeca6bf7/IDRD_A_2181746_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/d0eaff237afd/IDRD_A_2181746_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/13c0681b2510/IDRD_A_2181746_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/31b8b2b22599/IDRD_A_2181746_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/9f1da43bddd0/IDRD_A_2181746_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/ade10cfdc779/IDRD_A_2181746_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/ff3ed696ca41/IDRD_A_2181746_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/700262c87e18/IDRD_A_2181746_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/1bdd5d03ce21/IDRD_A_2181746_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/d69faeca6bf7/IDRD_A_2181746_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/d0eaff237afd/IDRD_A_2181746_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a517/9946320/13c0681b2510/IDRD_A_2181746_F0008_C.jpg

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