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

Authors :
Xu J
Cheng X
Tan L
Fu C
Ahmed M
Tian J
Dou J
Zhou Q
Ren X
Wu Q
Tang S
Zhou H
Meng X
Yu J
Liang P
Source :
Nano letters [Nano Lett] 2019 May 08; Vol. 19 (5), pp. 2914-2927. Date of Electronic Publication: 2019 Apr 19.
Publication Year :
2019

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.

Details

Language :
English
ISSN :
1530-6992
Volume :
19
Issue :
5
Database :
MEDLINE
Journal :
Nano letters
Publication Type :
Academic Journal
Accession number :
30929452
Full Text :
https://doi.org/10.1021/acs.nanolett.8b05202