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透明质酸负载 HSP90 抑制剂的杂化纳米粒子作为一种新型的皮下和原位结肠癌治疗的递药系统。

Hybrid Nanoparticles Modified by Hyaluronic Acid Loading an HSP90 Inhibitor as a Novel Delivery System for Subcutaneous and Orthotopic Colon Cancer Therapy.

机构信息

Department of Infectious Disease, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.

Department of Gastroenterology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Mar 2;16:1743-1755. doi: 10.2147/IJN.S275805. eCollection 2021.

DOI:10.2147/IJN.S275805
PMID:33688189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7936682/
Abstract

BACKGROUND

As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use.

METHODS

In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy.

RESULTS

Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs-17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs-17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo.

CONCLUSION

Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.

摘要

背景

作为癌症治疗的治疗靶点，HSP90 已被广泛研究。然而，HSP90 抑制剂 17AAG 的显著副作用限制了其临床应用。

方法

在这项研究中，我们使用透明质酸（HA）修饰的 DOTAP-PLGA 杂化纳米粒（HA-DOTAP-PLGA NPs）作为 17AAG 递送载体进行靶向结肠癌治疗。

结果

采用不同方法对这些杂化 PLGA NPs 的成功制备进行了表征。我们的结果表明，HA-NPs 在结肠癌细胞中的内化受 CD44 受体介导的内吞作用控制。Annexin V-propidium iodide 染色实验表明，HA-NPs-17AAG 诱导结肠癌细胞凋亡的效率高于游离 17AAG。在用于筛选抗癌功效的两种动物模型（Luc-HT29 皮下异种移植和 AOM/DSS 诱导的原位肿瘤模型）中，HA-NPs-17AAG 显著抑制了异种移植和原位肿瘤的生长，表明 HA-NPs-17AAG 比游离 17AAG 具有更好的治疗效果。值得注意的是，HA-DOTAP-PLGA NPs 在体外和体内均表现出良好的生物相容性。

结论

我们的研究为以 DOTAP-PLGA NPs 为创新药物递送系统的结肠癌治疗提供了临床前概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/11409a5dcd75/IJN-16-1743-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/c557c2c84798/IJN-16-1743-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/6e90f0dc2678/IJN-16-1743-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/681d348c2f89/IJN-16-1743-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/8ad18ec51fd5/IJN-16-1743-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/11409a5dcd75/IJN-16-1743-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/c557c2c84798/IJN-16-1743-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/2faaa7c8fdd9/IJN-16-1743-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/c922e162a65d/IJN-16-1743-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/852c17ef3fc7/IJN-16-1743-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/6e90f0dc2678/IJN-16-1743-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/681d348c2f89/IJN-16-1743-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/8ad18ec51fd5/IJN-16-1743-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b771/7936682/11409a5dcd75/IJN-16-1743-g0008.jpg

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