Hyaluronic Acid-Green Tea Catechin Micellar Nanocomplexes: Fail-safe Cisplatin Nanomedicine for the Treatment of Ovarian Cancer Without Off-Target Toxicity

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Hyaluronic Acid-Green Tea Catechin Micellar Nanocomplexes: Fail-safe Cisplatin Nanomedicine for the Treatment of Ovarian Cancer Without Off-Target Toxicity
Title:
Hyaluronic Acid-Green Tea Catechin Micellar Nanocomplexes: Fail-safe Cisplatin Nanomedicine for the Treatment of Ovarian Cancer Without Off-Target Toxicity
Journal Title:
Biomaterials
Keywords:
Publication Date:
22 September 2017
Citation:
Ki Hyun Bae, Susi Tan, Atsushi Yamashita, Wei Xia Ang, Shu Jun Gao, Shu Wang, Joo Eun Chung, Motoichi Kurisawa, Hyaluronic acid-green tea catechin micellar nanocomplexes: Fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity, Biomaterials, Volume 148, 2017, Pages 41-53, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2017.09.027.
Abstract:
The green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG), has gained significant attention as a potent adjuvant to enhance the antitumor efficacy of cisplatin while mitigating its harmful side effects. Herein we report the development of a fail-safe cisplatin nanomedicine constructed with hyaluronic acid-EGCG conjugate for ovarian cancer therapy. A simple mixing of this conjugate and cisplatin induces spontaneous self-assembly of micellar nanocomplexes having a spherical core-shell structure. The surface-exposed hyaluronic acid enables efficient delivery of cisplatin into CD44-overexpressing cancer cells via receptor-mediated endocytosis whereas the internally packed EGCG moieties offer an environment favorable for the encapsulation of cisplatin. In addition, the antioxidant effect of EGCG moieties ensures fail-safe protection against off-target organ toxicity originating from cisplatin-evoked oxidative stress. Pharmacokinetic and biodistribution studies reveal the prolonged blood circulation and preferential tumor accumulation of intravenously administered nanocomplexes. Moreover, the nanocomplexes exhibit superior antitumor efficacy over free cisplatin while displaying no toxicity in both a subcutaneous xenograft model and peritoneal metastatic model of human ovarian cancer. Our findings demonstrate proof of concept for the feasibility of green tea catechin-based micellar nanocomplexes as a safe and effective cisplatin nanomedicine for ovarian cancer treatment.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research is supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research (A*STAR), Singapore).
Description:
ISSN:
0142-9612
1878-5905
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