Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy.

Content Provider	Europe PMC
Author	Liao, Han Zhao, Shan Wang, Huihui Liu, Yang Zhang, Ying Sun, Guangwei
Copyright Year	2019
Abstract	BackgroundAmphiphilic fusion drugs are covalent conjugates of a lipophilic drug and a hydrophilic drug or their active fragments. These carrier-free self-assembly nanomaterials are helpful to co-deliver two synergic drugs to the same site regardless of pharmacokinetic properties of individual drugs. Retinoic hydroxamic acid (RHA) is a “fusion drug” of all-trans retinoic acid (ATRA) and vorinostat, a histone deacetylase (HDAC) inhibitor showing synergic effect with ATRA on cancer therapy. Although RHA was synthesized in 2005, its nanoscale self-assembly property, anticancer activity, and possible related mechanism are still unclear.MethodsRHA nanoparticles were observed under transmission electron microscope (TEM). Both in vitro cell viability, colony formation assay, and in vivo xenograft mouse tumor model were employed here to study anticancer activity of RHA nanoparticles. The putative synergic anticancer mechanism of activating retinoic acid receptor (RAR) and inhibiting HDAC were investigated via receptor inhibitor rescue assay and in vitro enzyme activity assay, respectively.ResultsRHA could form nanoparticle formation by self-assembly and abrogates growth of several solid tumor cell lines even after RHA nanoparticles' washout. However, opposite to our initial hypothesis, pre-treating the melanoma cells with RAR antagonists showed no impact on inhibitory effect of RHA nanoparticles, which suggested that the target of the molecule on melanoma cells is not RAR and retinoid X receptor (RXR). Importantly, RHA nanoparticles inhibited the growth of xenograft tumors without obvious impact on haematological indexes and hepatorenal function of these tumor-bearing mice.ConclusionOur findings demonstrate the promise of RHA nanoparticles in treating malignant melanoma tumors with high efficacy and low toxicity.
Page Count	11
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	14
PubMed Central reference number	PMC6778447
PubMed reference number	31632011
e-ISSN	11782013
DOI	10.2147/ijn.s196974
Language	English
Publisher	Dove Medical Press
Publisher Date	2019-10-01
Access Restriction	Open
Rights License	This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). © 2019 Liao et al.
Subject Keyword	nano-drugs self-assembly retinoid cancer therapy melanoma
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science