Original Article
Near infra-red laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods with reduced cardiotoxicity in swiss albino mice

https://doi.org/10.1016/j.nano.2015.03.012Get rights and content

Abstract

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/cm2 laser irradiation. In conclusion, multifunctional DOX@PSS-GNR with improved therapeutic index and reduced cardiotoxicity represents a promising candidate for cancer treatment.

From the 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.

Graphical Abstract

NIR laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods against Dalton lymphoma ascites tumor with reduced cardiotoxicity in Swiss albino mice.

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Section snippets

Synthesis and characterization of DOX@PSS-GNR

Monodisperse GNR was synthesized using the silver ion-assisted seed mediated growth method and were surface modified with anionic PSS as described in our previous report.20 The detailed methodology for synthesis and characterization of DOX@PSS-GNR is provided in supporting information. For all dilutions, DOX@PSS-GNR was dispersed in phosphate buffered saline (pH = 7.4).

Animals and tumor models

Six to eight week old male Swiss albino mice (20-25 g BW) were purchased from IISC Bangalore, India and were maintained in the

Results

In the present study, we demonstrate the in vivo antitumor effect of DOX@PSS-GNR along with its photothermal efficiency against DLA tumor in Swiss albino mice. Synthesis and characterization of DOX@PSS-GNR have been briefly explained in the supporting information. Preliminary results of the study indicate the highly biocompatible nature of DOX@PSS-GNR with excellent in vitro stability in serum sample as evidenced by hemolytic assay (Figure SI). The loading efficiency of DOX molecule on GNR-PSS

Discussion

Recently we reported a multifunctional DOX delivery system by conjugating doxorubicin with GNR via poly (sodium 4-styrensulfonate) (PSS) and found it to be highly biocompatible with excellent anticancer potential against human breast cancer cells, in vitro.20 In continuation of the study, herein we investigate the in vivo antitumor and photothermal efficacy of DOX@PSS-GNR along with its potential impact on cardiotoxicity in Swiss albino mice. The entire study has been carried out employing a

Acknowledgment

The authors are grateful to Ms. H. Kalpana, Mr. S. Venkatesh and Mr. V. Raju (Department of Basic Medical Science and Physics, Bharathidasan University, Tiruchirappalli) for technical support.

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    Source of Support: This work was supported by the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India, New Delhi, India under the grant no. BT/PR12864/NNT/28/442/2009.

    Conflict of interest statement: None of the authors declare a conflict of interest.

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