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Nano Lett. 2019 May 8;19(5):2914-2927. doi: 10.1021/acs.nanolett.8b05202. Epub 2019 Apr 19.

Microwave Responsive Nanoplatform via P-Selectin Mediated Drug Delivery for Treatment of Hepatocellular Carcinoma with Distant Metastasis.

Author information

1
Department of Interventional Ultrasound , Chinese PLA General Hospital , Beijing 100853 , China.
2
CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry , Chinese Academy of Sciences , Beijing 100190 , China.
3
State Key Laboratory of Kidney Disease , Chinese PLA General Hospital , Beijing 100853 , China.
4
Department of Ultrasound , Sichuan Provincial Cancer Hospital , Sichuan 610041 , China.
5
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology , Beth Israel Deaconess Medical Center/Harvard Medical School , Boston , Massachusetts 02215 , United States.
6
CAS Key Laboratory of Molecular Imaging, Institute of Automation , Chinese Academy of Sciences , Beijing 100190 , China.

Abstract

Hepatocellular carcinoma (HCC) with metastatic disease is associated with a low survival in clinical practice. Many curative options including liver resection, transplantation, and thermal ablation are effective in local but limited for patients with distant metastasis. In this study, the efficacy, specificity, and safety of P-selectin targeted delivery and microwave (MW) responsive drug release is investigated for development of HCC therapy. By encapsulating doxorubicin (DOX) and MW sensitizer (1-butyl-3-methylimidazolium-l-lactate, BML) into fucoidan conjugated liposomal nanoparticles (TBP@DOX), specific accumulation and prominent release of DOX in orthotopic HCC and lung metastasis are achieved with adjuvant MW exposure. This results in orthotopic HCC growth inhibition that is not only 1.95-fold higher than found for nontargeted BP@DOX and 1.6-fold higher than nonstimuli responsive TP@DOX but is also equivalent to treatment with free DOX at a 10-fold higher dose. Furthermore, the optimum anticancer efficacy against distant lung metastasis and effective prevention of widespread dissemination with a prolonged survival is described. In addition, no adverse metabolic events are identified using the TBP@DOX nanodelivery system despite these events being commonly observed with traditional DOX chemotherapy. Therefore, administering TBP@DOX with MW exposure could potentially enhance the therapeutic efficacy of thermal-chemotherapy of HCC, especially those in the advanced stages.

KEYWORDS:

Nanoplatform; P-selectin; hepatocellular carcinoma; metastasis; microwave

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