Effects of Near-infrared Laser Irradiation of Biodegradable Microspheres Containing Hollow Gold Nanospheres and Paclitaxel Administered Intraarterially in a Rabbit Liver Tumor Model

Abstract

PurposeTo evaluate the effects of near-infrared (NIR) laser irradiation of microspheres (MS) containing hollow gold nanospheres (HAuNS) and paclitaxel (PTX) administered intraarterially in an animal model. Materials and MethodsFor the ex vivo experiments, VX2 tumor–bearing rabbits underwent administration of MS-HAuNS or MS via the hepatic artery (HA). The animals were killed, the liver tumors were subjected to NIR irradiation, and temperature changes were estimated with magnetic resonance (MR) imaging. For the in vivo study, VX2 tumor–bearing rabbits were randomly assigned to three groups: MS-HAuNS-PTX-plus-NIR, MS-HAuNS-PTX, and saline-plus-NIR. Laser irradiation was delivered at 1 hour and at 3 days after administration of saline or MS-HAuNS-PTX via the HA. Animals were euthanized, and tumors were analyzed for necrosis and apoptosis. Plasma samples were collected from the MS-HAuNS-PTX-plus-NIR animals for PTX analysis. ResultsEx vivo experiments showed intratumoral heating in animals that received MS-HAuNS but no temperature change in animals that received MS. Animals treated with MS-HAuNS-PTX-plus-NIR showed a transient increase in plasma PTX levels after each NIR irradiation and significantly greater tumor necrosis than animals that received MS-HAuNS-PTX or saline-plus-NIR (44.9% vs 13.8% or 23.7%; P < .0001). The mean apoptotic index in the MS-HAuNS-PTX-plus-NIR group (5.01 ± 1.66) was significantly higher than the mean apoptotic index in the MS-HAuNS-PTX (2.99 ± 0.97) or saline-plus-NIR (1.96 ± 0.40) groups (P = .0013). ConclusionsNIR laser irradiation after MS-HAuNS-PTX administration results in intratumoral heating and increases the efficacy of treatment. Further studies are required to evaluate the optimal laser settings to maximize therapeutic efficacy.