Neutrophil-Mediated Clinical Nanodrug for Treatment of Residual Tumor After Focused Ultrasound Ablation

Abstract Background: The risk of local recurrence of high intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. Combination of HIFU with traditional chemotherapy still remains the unsatisfactory outcome because of off-site drug uptake.Results: Herein, we proposed the strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeting therapy for residual tumor of HIFU ablation. Neutrophils as a carrier, and PEGylated liposome doxorubicin (PLD) as a nanodrug model of chemotherapy, were selected to form an innovative cell therapy drug (PLD@NEs). The targeting performance and therapeutic potential of PLD@NEs were evaluated using hepa1-6 cells and corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation, and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy.Conclusion: This effective integration takes full use of the advantages of both HIFU, chemotherapy and neutrophil, attracting more focus on the practice of improving the existing clinical therapeutics.

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Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01087-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jian Shen ◽

Junnian Hao ◽

Yini Chen ◽

Hairong Liu ◽

Jianrong Wu ◽

...

Keyword(s):

Focused Ultrasound ◽

Therapeutic Potential ◽

Malignant Tumors ◽

Residual Tumor ◽

High Intensity Focused Ultrasound ◽

Drug Uptake ◽

Integrated Method ◽

Hifu Ablation ◽

Inflammatory Stimuli ◽

Ultrasound Ablation

Abstract Background The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake. Results Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy. Conclusions This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies. Graphical Abstract

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Acoustic Cavitation Enhances Focused Ultrasound Ablation with Phase-Shift Inorganic Perfluorohexane Nanoemulsions: AnIn VitroStudy Using a Clinical Device

BioMed Research International ◽

10.1155/2016/7936902 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Lu-Yan Zhao ◽

Jian-Zhong Zou ◽

Zong-Gui Chen ◽

Shan Liu ◽

Jiao Jiao ◽

...

Keyword(s):

Phase Shift ◽

Focused Ultrasound ◽

Continuous Wave ◽

Acoustic Cavitation ◽

High Intensity Focused Ultrasound ◽

Inertial Cavitation ◽

Hifu Ablation ◽

Duty Cycles ◽

Ultrasound Ablation ◽

Phosphate Buffered Saline

Purpose.To investigate whether acoustic cavitation could increase the evaporation of a phase-shift inorganic perfluorohexane (PFH) nanoemulsion and enhance high intensity focused ultrasound (HIFU) ablation.Materials and Methods.PFH was encapsulated by mesoporous silica nanocapsule (MSNC) to form a nanometer-sized droplet (MSNC-PFH). It was added to a tissue-mimicking phantom, whereas phosphate buffered saline (PBS) was added as a control (PBS-control). HIFU (Pac=150 W,t=5/10 s) exposures were performed in both phantoms with various duty cycles (DC). US images, temperature, and cavitation emissions were recorded during HIFU exposure. HIFU-induced lesions were measured and calculated.Results.Compared to PBS-control, MSNC-PFH nanoemulsion could significantly increase the volume of HIFU-induced lesion (P<0.01). Peak temperatures were 78.16 ± 5.64°C at a DC of 100%, 70.17 ± 6.43°C at 10%, 53.17 ± 4.54°C at 5%, and 42.00 ± 5.55°C at 2%, respectively. Inertial cavitation was much stronger in the pulsed-HIFU than that in the continuous-wave HIFU exposure. Compared to 100%-DC exposure, the mean volume of lesion induced by 5 s exposure at 10%-DC was significantly larger, but smaller at 2%-DC.Conclusions.MSNC-PFH nanoemulsion can significantly enhance HIFU ablation. Appropriate pulsed-HIFU exposure could significantly increase the volume of lesion and reduce total US energy required for HIFU ablation.

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