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靶向前药自组装纳米粒子用于癌症治疗。

Targeted Prodrug-Based Self-Assembled Nanoparticles for Cancer Therapy.

机构信息

Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Key Laboratory of Spin Electron and Nanomaterials of Anhui Higher Education Institutes, Suzhou University, Suzhou 234000, People's Republic of China.

Department of Pharmaceutical Analysis, School of Pharmacy, Nanjing Medical University, Nanjing 211166, People's Republic of China.

出版信息

Int J Nanomedicine. 2020 Apr 24;15:2921-2933. doi: 10.2147/IJN.S247443. eCollection 2020.

DOI:10.2147/IJN.S247443
PMID:32425524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7187935/
Abstract

BACKGROUND

Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic.

METHODS AND RESULTS

In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects.

CONCLUSION

This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.

摘要

背景

靶向前药作为肿瘤治疗的药物制剂具有多种应用。因此，两性小分子前药与纳米特性相结合，用于自组装纳米药物递送系统（DDS）是一个非常有趣的研究课题。

方法和结果

在本研究中，我们通过整合靶向小分子和具有规则结构和完美靶向能力的纳米 DDS，开发了一种前药自组装纳米平台，即 2-葡糖胺-荧光素-5（6）-异硫氰酸酯-谷氨酸-紫杉醇（2DA-FITC-PTX NPs）。2-葡糖胺（DA）和紫杉醇通过氨基酸基团连接作为靶向配体和抗肿瘤化疗药物。2-DA 分子结构可以增强基于前药的 2DA-FITC-PTX NPs 的靶向能力并延长保留时间，从而降低正常细胞/组织的毒性。基于前药的 DDS 中的荧光染料 FITC 或近红外荧光染料 ICG 吸引了体内光学成像，以研究 2DA-FITC-PTX NPs 的行为。体外和体内结果证明，2DA-FITC-PTX NPs 表现出优异的靶向能力、抗癌活性和较弱的副作用。

结论

这项工作展示了一种新的化疗纳米材料组合，可能会促进基于前药的 DDS 在未来的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/f51303972463/IJN-15-2921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/66b19388fc73/IJN-15-2921-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/6bf78ae3e083/IJN-15-2921-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/f36ce2b6b249/IJN-15-2921-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/6acdff708675/IJN-15-2921-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/82e6ab52dfac/IJN-15-2921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/f51303972463/IJN-15-2921-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/66b19388fc73/IJN-15-2921-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/6bf78ae3e083/IJN-15-2921-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/f36ce2b6b249/IJN-15-2921-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/6acdff708675/IJN-15-2921-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/82e6ab52dfac/IJN-15-2921-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b9/7187935/f51303972463/IJN-15-2921-g0006.jpg

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