Near infra-red laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods with reduced cardiotoxicity in swiss albino mice
Near infra-red laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods with reduced cardiotoxicity in swiss albino mice
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DOI：
10.1016/j.nano.2015.03.012
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Premkumar, Kumpati
中科院分区：
文献类型：
--
作者：
Arunkumar, Pitchaimani;Raju, Baskar;Premkumar, Kumpati
开发一种既无副作用又不影响疗效的多功能给药系统是抗癌研究中的一个重要问题。最近，我们开发并展示了阿霉素偶联的金纳米棒(DOX@PSS-GNR)作为一种持续的药物输送载体。在这里，我们研究了DOX@PSS-GNR的生物分布、抗肿瘤和光热效应以及它在体内对心脏毒性的潜在影响。研究表明，在DOX@PSS-GNR动物中，心肌中游离DOX的累积减少了4倍，这通过保存心脏标志物来减少心脏损伤，从而进一步将其心脏毒性降至最低。此外，DOX@PSS-GNR对Dalton淋巴瘤腹水(DLA)显示出有效的抗肿瘤效果，细胞周期分析、细胞凋亡信号以及肿瘤体积和重量的减少都证明了这一点。此外，DOX@PSS-GNR在0.1W/cm(2)激光照射下表现出较高的光热响应，并主导DLA的生长。综上所述，多功能DOX@PSS-GNR具有改善治疗指数和降低心脏毒性的特点，是一种很有前途的癌症治疗候选药物。然而，尽管脂质体制剂的发展，副作用仍然是显著的。在这项研究中，作者研究了阿霉素偶联金纳米棒(DOX@PSS-GNR)的生物分布、抗肿瘤活性和全身副作用。新给药系统的心脏毒性大大降低，应该为未来的临床使用提供一种改进的制剂。(C)2015 Elsevier Inc.保留所有权利。
Development of a multifunctional drug delivering system without side effects and compromising its therapeutic efficacy is a major concern in anticancer research. Recently, we have developed and demonstrated doxorubicin conjugated gold nanorod (DOX@PSS-GNR) as a sustained drug delivery vehicle. Here, we investigate the biodistribution, antitumor and photothermal efficacy of DOX@PSS-GNR along with its potential impact on cardiotoxicity in in vivo. The studies revealed that the accumulation of Free DOX in myocardium was 4-fold reduced in DOX@PSS-GNR animals, which further minimizes its cardiotoxicity by decreasing cardiac injury via preservation of cardiac markers. Further, DOX@PSS-GNR exhibits effective antitumor efficacy against Dalton lymphoma ascites (DLA) as evidenced by cell cycle analysis, apoptotic signals and reduced tumor volume and weight. In addition, DOX@PSS-GNR exhibits higher photothermal response and dominates DLA growth upon 0.1 W/cm(2) laser irradiation. In conclusion, multifunctional DOX@PSS-GNR with improved therapeutic index and reduced cardiotoxicity represents a promising candidate for cancer treatment.Fromthe Clinical Editor: Doxorubicin is a widely used agent for cancer therapy. However, the side effects are still significant, despite the development of liposomal formulation. In this study, the authors investigated the use of doxorubicin conjugated gold nanorods (DOX@PSS-GNR) in terms of biodistribution, antitumor activity and systemic side effects. The much reduced cardiotoxicity of the new delivery system should provide an improved agent for future clinical use. (C) 2015 Elsevier Inc. All rights reserved.