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

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 0.1W/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 EditorDoxorubicin 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.