Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 13, Issue -, Pages 5673-5683Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S161203
Keywords
anti-lymphoma activity; targeted therapy; doxorubicin-loaded; dextran; nano-carrier; cardiac toxicity
Funding
- National Natural Science Foundation of China [81830007, 81520108003, 81670716, 81201863, 21374061]
- Shanghai Commission of Science and Technology [14430723400, 14140903100, 14520710300, 16JC1405800]
- Shanghai Municipal Education Commission Gao Feng Clinical Medicine Grant Support [20152206, 20152208]
- Interdisciplinary Program of Shanghai Jiao Tong University [YG2014QN16]
- Chang Jiang Scholars Program
Ask authors/readers for more resources
Purpose: Cardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity. Methods: Inspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH) as much as that in systemic circulation condition (pH 7.4). Results: Lymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2. Conclusion: Dox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available