Investigation of Nanodrug Combined with Ultrasound Hyperthermia and Thermal Ablation for Tumor Treatment
Date Issued
2015
Date
2015
Author(s)
Chiu, Li-Chen
Abstract
Background: Anti-cancer nanodrugs can pass through leaky tumor vessels to achieve therapeutic purposes. When the tumor volume is large, the interior part forms coagulation necrosis, resulting in increased interstitial pressure and distance between blood vessels to hinder drug transport. Purpose: The purpose of this study is to combine nanodrug(PLD) with ultrasound hyperthermia to enhance the drug delivery in the peripheral region of tumors, and ultrasound ablation surgery for poor circulation region to achieve the overall treatment efficacy. Materials and methods: In this study, BALB/c female mice weighting from 18 to 22 g were used. Murine breast cancer cells 4T1(106 cells) were subcutaneously implanted into the mice''s back. Hyperthermia was induced by a 1-MHz plane ultrasound transducer, and ablation surgery was conducted by a 0.47-MHz focus ultrasound transducer. Experimental groups were divided into two parts: 5 mg PLD/kg and 3 mg PLD/kg. Each part was divided into four groups: control group, PLD group, PLD+hyperthermia(42°C 10 min) group, and PLD+ablation(56°C)+hyperthermia group. When the tumor grew up to 250-350 mm3, the first treatment was conducted, and five days later for the second treatment. Body weight and tumor volume were measured every day. The tumor change was also quantified by In-Vivo Image System(IVIS) before and after the treatments. H&E histological staining was also used to analyze the tumor tissues. Results: The tumors treated with 5 mg PLD/kg were significantly smaller than the control group. The tumor size of the PLD+hyperthermia group was significantly smaller than the PLD group. However, there was no significant difference between the PLD+hyperthermia group and the PLD+ablation+hyperthermia group. When the PLD dose was reduced to 3 mg/kg, the tumors treated with PLD were smaller than the control group. The tumor size of the PLD+ablation+hyperthermia group was significantly smaller than the PLD+hyperthermia group. The result of IVIS image showed that both 5 mg PLD/kg and 3 mg PLD/kg resulted in lower photon signals than the control group. The groups conducted with additional ultrasound therapy showed lower photon signals than the PLD alone group. Nevertheless, there was no significant difference between the PLD+ablation+hyperthermia group and the PLD+hyperthermia group. The H&E tumor histological staining showed that hyperthermia could induce inflammation, and the ablated tumor tissues were seriously destroyed and looser than the other three groups. Conclusion: Hyperthermia could increase nanodrug accumulation in tumor tissues and improve therapeutic efficacy. When a high dose of nanodrug(5 mg/kg) was used, additional ablation could not significantly improve therapeutic results. On the other side, the combination of hyperthermia and ablation could significantly enhance the treatment efficacy for a low dose of nanodrug(3 mg/kg).
Subjects
tumor treatment
nanodrug
ultrasound
hyperthermia
ablation
SDGs
Type
thesis
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