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Microwave Responsive Nanoplatform via P-Selectin Mediated Drug Delivery for Treatment of Hepatocellular Carcinoma with Distant Metastasis.
- 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.
- Subjects :
- Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Doxorubicin
Drug Delivery Systems
Drug Liberation
Humans
Lactates chemistry
Lactates pharmacology
Liposomes chemistry
Liposomes pharmacology
Liver Neoplasms pathology
Lung Neoplasms secondary
Microwaves
Nanoparticles chemistry
Neoplasm Metastasis
P-Selectin chemistry
Carcinoma, Hepatocellular drug therapy
Liver Neoplasms drug therapy
Lung Neoplasms drug therapy
P-Selectin antagonists & inhibitors
Subjects
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