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靶向氮芥的聚乙二醇化金纳米棒的研制及其用于荷瘤小鼠的表阿霉素化学-光热治疗。

Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumor-bearing mice.

机构信息

School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China,

Department of Pharmacy, The General Hospital of FAW, Changchun 130011, China.

出版信息

Int J Nanomedicine. 2019 Mar 8;14:1817-1833. doi: 10.2147/IJN.S192520. eCollection 2019.

DOI:10.2147/IJN.S192520
PMID:30880982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6413758/
Abstract

BACKGROUND

Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects.

METHODS

In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au-CTAB-PAA-PEG-AA.EPI complex.

RESULTS

The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice.

CONCLUSION

These results demonstrate a promising strategy for clinical application of CPTT in cancer.

摘要

背景

金纳米棒（AuNRs）由于其光学和电子特性，即表面等离子体共振，已被开发用于实现癌症的光介导光热疗法（PTT）。然而，单独的 PTT 可能会导致肿瘤杀伤效率低下。最近，PTT 与化学疗法的结合已被用于实现协同抗癌效果。

方法

在本研究中，制备了十六烷基三甲基溴化铵（CTAB）、聚丙烯酸（PAA）和聚乙二醇化的苯甲酰胺（一种已知靶向 sigma 受体的配体）包覆的金纳米棒（AuNRs），以产生一系列带负电荷的苯甲酰胺靶向聚乙二醇化金纳米棒（称为 Au-CTAB-PAA-PEG-AA），用于 PTT 和化学疗法的联合治疗（称为化疗光热治疗 [CPTT]）。阿霉素（EPI，一种蒽环类药物）通过静电相互作用有效地负载在 Au-CTAB-PAA-PEG-AA 的表面上，形成 Au-CTAB-PAA-PEG-AA.EPI 复合物。

结果

所得复合物表现出 pH 依赖性药物释放，促进了 EPI 的核内转运，并在人前列腺癌 PC-3 细胞中诱导了抗增殖作用。当 Au-CTAB-PAA-PEG-AA.EPI 复合物进一步用所需的激光照射刺激时，在 PC-3 异种移植小鼠中观察到协同作用。

结论

这些结果表明 CPTT 在癌症临床应用中的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/483730cfaf1e/ijn-14-1817Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/503590a22c11/ijn-14-1817Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/56d495b45b40/ijn-14-1817Fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/29e941f14b95/ijn-14-1817Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/cc158aa11d05/ijn-14-1817Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/16e2decd992f/ijn-14-1817Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/963b5efd1b04/ijn-14-1817Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/483730cfaf1e/ijn-14-1817Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/503590a22c11/ijn-14-1817Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/56d495b45b40/ijn-14-1817Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/96702a91256e/ijn-14-1817Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/29e941f14b95/ijn-14-1817Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/cc158aa11d05/ijn-14-1817Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/16e2decd992f/ijn-14-1817Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/963b5efd1b04/ijn-14-1817Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d90/6413758/483730cfaf1e/ijn-14-1817Fig8.jpg

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