Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy

Rahul A Sheth,Marites P Melancon,Junjie Li,Xiaoxia Wen,Elizabeth M Whitley,Sanjay Gupta,Xin Ji,Diana S.-L Chow,Cheng-Hui Hsiao,Chun Li,Y Andrew Wang

doi:10.1186/s12645-020-00062-8

Abstract

BackgroundDoxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Adult New Zealand white rabbits (N = 25) were inoculated with VX2 tumors into the left lobe of the liver. The animals were then randomized to sham surgery (N = 5), PTA only (N = 3), Dox@HAuNS only (N = 5), HAuNS + PTA (N = 5), and Dox@HAuNS + PTA (N = 7). Nanoparticles were delivered as an emulsion with Lipiodol (Guerbet, France) via a trans-arterial approach. Following nanoparticle delivery, PTA was performed using an 808-nm fibered laser at 1.5 W for 3 min. Thermography during PTA demonstrated a sustained elevation in tumoral temperature in both HAuNS + laser and Dox@HAuNS + laser treatment groups relative to animals that underwent laser treatment without prior nanoparticle delivery.ResultsThere was a significant decrease in tumor volumes in all three treatment arms relative to control arms (P = 0.004). Concentrations of intratumoral doxorubicin were significantly greater in animals treated with laser compared to those that were not treated with laser (P < 0.01).ConclusionsDoxorubicin-loaded HAuNS is a promising therapeutic agent for dual ablation/chemoembolization treatment of liver cancer.

Highlights

Doxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation
Sheth et al Cancer Nano (2020) 11:6 published randomized trials demonstrating survival advantages with Transarterial chemoembolization (TACE) over embolization alone and conservative management, respectively. This level 1 evidence led to the incorporation of TACE as standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer (BCLC) system
The purpose of this study was to evaluate the effects of HAuNS-mediated localized Dox delivery and photothermal ablation (PTA) on tumor growth when delivered intra-arterially in a rabbit model of liver tumor

Summary

Introduction

Doxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Transarterial chemoembolization (TACE) and thermal ablation are cornerstones in the management of hepatocellular carcinoma (HCC) Both are incorporated into the most commonly used treatment guidelines and are considered the standard of care for earlystage and intermediate-stage HCC. Sheth et al Cancer Nano (2020) 11:6 published randomized trials demonstrating survival advantages with TACE over embolization alone and conservative management, respectively. This level 1 evidence led to the incorporation of TACE as standard of care for patients with intermediate-stage HCC by the Barcelona Clinic Liver Cancer (BCLC) system. For TACE, microenvironmental barriers to drug delivery diminish treatment efficacy (Sheth et al 2013)

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