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Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy.
Int J Nanomedicine 2019; 14:7963-7973IJ

Abstract

Background

Amphiphilic 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.

Methods

RHA 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.

Results

RHA 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.

Conclusion

Our findings demonstrate the promise of RHA nanoparticles in treating malignant melanoma tumors with high efficacy and low toxicity.

Authors+Show Affiliations

Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31632011

Citation

Liao, Han, et al. "Self-Assembly of Retinoid Nanoparticles for Melanoma Therapy." International Journal of Nanomedicine, vol. 14, 2019, pp. 7963-7973.
Liao H, Zhao S, Wang H, et al. Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy. Int J Nanomedicine. 2019;14:7963-7973.
Liao, H., Zhao, S., Wang, H., Liu, Y., Zhang, Y., & Sun, G. (2019). Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy. International Journal of Nanomedicine, 14, pp. 7963-7973. doi:10.2147/IJN.S196974.
Liao H, et al. Self-Assembly of Retinoid Nanoparticles for Melanoma Therapy. Int J Nanomedicine. 2019;14:7963-7973. PubMed PMID: 31632011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Self-Assembly Of Retinoid Nanoparticles For Melanoma Therapy. AU - Liao,Han, AU - Zhao,Shan, AU - Wang,Huihui, AU - Liu,Yang, AU - Zhang,Ying, AU - Sun,Guangwei, Y1 - 2019/10/01/ PY - 2018/12/05/received PY - 2019/07/27/accepted PY - 2019/10/22/entrez PY - 2019/10/22/pubmed PY - 2019/10/22/medline KW - cancer therapy KW - melanoma KW - nano-drugs KW - retinoid KW - self-assembly SP - 7963 EP - 7973 JF - International journal of nanomedicine JO - Int J Nanomedicine VL - 14 N2 - Background: Amphiphilic 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. Methods: RHA 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. Results: RHA 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. Conclusion: Our findings demonstrate the promise of RHA nanoparticles in treating malignant melanoma tumors with high efficacy and low toxicity. SN - 1178-2013 UR - https://www.unboundmedicine.com/medline/citation/31632011/Self-Assembly_Of_Retinoid_Nanoparticles_For_Melanoma_Therapy L2 - https://dx.doi.org/10.2147/IJN.S196974 DB - PRIME DP - Unbound Medicine ER -