Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer.

Abstract

Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle (NP) surfaces with ligands and/or additional polymeric layers. In this work, we developed DTX-loaded formulations using polydopamine-modified NPs synthesized using D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. The size and morphology of pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs changed obviously compared with TPGS-PLA/NPs. In vitro studies showed that TPGS-PLA/NPs, pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs had similar release profiles of DTX. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency in liver cancer cell line HepG2. Moreover, DTX-loaded Gal-pD-TPGS-PLA/NPs inhibited the growth of HepG2 cells more potently than TPGS-PLA/NPs, pD-TPGS-PLA/NPs, and a clinically available DTX formulation (Taxotere®). The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they may be used as a potentially eligible drug delivery system targeting liver cancers.

STATEMENT OF SIGNIFICANCE:

Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle surfaces with ligands and/or additional polymeric layers. In this work, we developed docetaxel (DTX)-loaded formulations using polydopamine-modified NPs synthesized from D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency for liver cancer cell line HepG2. The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they could be used as a potentially eligible drug delivery system targeting liver cancers.

• Authors: Dunwan Zhu, Wei Tao, Hongling Zhang, Gan Liu, Teng Wang, Linhua Zhang, Xiaowei Zeng, Lin Mei
• Journal: Acta biomaterialia (Acta Biomater) Vol. 30 Pg. 144-154 (Jan 2016) ISSN: 1878-7568 [Electronic] England
• PMID: 26602819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Indoles
• Polyesters
• Polymers
• Taxoids
• polydopamine
• Vitamin E
• Docetaxel
• Lactic Acid
• Polyethylene Glycols
• poly(lactide)
• tocophersolan

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Docetaxel
• Drug Delivery Systems (methods)
• Hep G2 Cells
• Humans
• Indoles (chemistry, pharmacokinetics, pharmacology)
• Lactic Acid (chemistry, pharmacokinetics, pharmacology)
• Liver Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• Polyesters
• Polyethylene Glycols (chemistry, pharmacokinetics, pharmacology)
• Polymers (chemistry, pharmacokinetics, pharmacology)
• Taxoids (chemistry, pharmacokinetics, pharmacology)
• Vitamin E (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Xenograft Model Antitumor Assays