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一种联合自组装药物递送系统用于有效的抗乳腺癌治疗。

A Combined Self-Assembled Drug Delivery for Effective Anti-Breast Cancer Therapy.

机构信息

School of Pharmacy, Bengbu Medical College, Bengbu, 233030, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Mar 23;16:2373-2388. doi: 10.2147/IJN.S299681. eCollection 2021.

DOI:10.2147/IJN.S299681
PMID:33790555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8001668/
Abstract

AIM

The metastasis of breast cancer is an important cause of tumor recurrence. This study highlights that tyrosine kinase inhibitors dasatinib (DAS) and rosiglitazone (ROZ) inhibit tumor growth and reduce the occurrence of tumor cell metastasis. Due to the poor water solubility, short half-time in the body of DAS and ROZ, which increases the difficulty of tumor treatment, as well as the demand for nano-drug delivery systems for organ-specific therapies.

METHODS

Hyaluronic acid (HA) and DAS are bonded by a pH-sensitive ester bond to form an HA-DAS polymer. Then, ROZ was added as the core, D-A-tocopherol polydiethylene glycol isosuccinate (TPGS) and HA-DAS were used as carriers to form HA-DAS and TPGS mixed micelle system loaded with ROZ (THDR-NPs). The size and structure of THDR-NPs were characterized, the drug release, stability and biosafety of THDR-NPs were studied. In vitro, the cytotoxicity, targeting effect and tumor metastasis inhibition of THDR-NPs were evaluated in human breast cancer cell lines. In addition, the selective potency of designed THDR-NPs in depleting was further verified in vivo in the tumor-bearing nude mice model.

RESULTS

The designed THDR-NPs have a particle size of less than 100 nm, good stability, biological safety and sustained release, and showed strong therapeutic effects on breast cancer models in vitro and in vivo. Moreover, it has been proved that THDR-NPs have the ability to inhibit tumor metastasis.

CONCLUSION

DAS and ROZ were designed into micelles, the efficacy of THDR-NPs was higher than that of free drugs. These results indicate that nanoparticles have a good application prospect in the treatment of tumor metastasis.

摘要

目的

乳腺癌的转移是肿瘤复发的一个重要原因。本研究强调了酪氨酸激酶抑制剂达沙替尼（DAS）和罗格列酮（ROZ）抑制肿瘤生长和减少肿瘤细胞转移的发生。由于 DAS 和 ROZ 的水溶性差、体内半衰期短，这增加了肿瘤治疗的难度，以及对用于器官特异性治疗的纳米药物输送系统的需求。

方法

透明质酸（HA）与 DAS 以 pH 敏感酯键结合形成 HA-DAS 聚合物。然后，加入 ROZ 作为核心，D-A-生育酚聚乙二醇琥珀酸酯（TPGS）和 HA-DAS 作为载体，形成负载 ROZ 的 HA-DAS 和 TPGS 混合胶束系统（THDR-NPs）。对 THDR-NPs 的粒径和结构进行了表征，研究了 THDR-NPs 的药物释放、稳定性和生物安全性。体外，评估了 THDR-NPs 在人乳腺癌细胞系中的细胞毒性、靶向作用和肿瘤转移抑制作用。此外，还在荷瘤裸鼠模型中进一步验证了设计的 THDR-NPs 在耗竭方面的选择性。

结果

设计的 THDR-NPs 的粒径小于 100nm，具有良好的稳定性、生物安全性和持续释放性，在体外和体内对乳腺癌模型表现出强烈的治疗效果。此外，已经证明 THDR-NPs 具有抑制肿瘤转移的能力。

结论

将 DAS 和 ROZ 设计成胶束，THDR-NPs 的疗效高于游离药物。这些结果表明，纳米粒子在肿瘤转移的治疗中有很好的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/a96410ee87e3/IJN-16-2373-g0013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/a96410ee87e3/IJN-16-2373-g0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/eedbb6b4f856/IJN-16-2373-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/6db7ec6655b7/IJN-16-2373-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/37c9182b0439/IJN-16-2373-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/d05d1d150d8a/IJN-16-2373-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/61d1bde30627/IJN-16-2373-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/50685c1d532c/IJN-16-2373-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/808c3b680163/IJN-16-2373-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/6431e54a4fbb/IJN-16-2373-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/f83d140c19db/IJN-16-2373-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae2/8001668/42e5ac7f9a6a/IJN-16-2373-g0011.jpg
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