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Versatile redox-sensitive pullulan nanoparticles for enhanced liver targeting and efficient cancer therapy.

Abstract
A reversibly disulfide-crosslinked pullulan nanoparticle with folic acid (FA) decoration (FA-Pull-LA CLNPs) was fabricated for dual-targeted and reduction-responsive anti-tumoral liver drug delivery based on the specific affinity of pullulan and FA to overexpress asialoglycoprtein receptors (ASGPR) and folate receptors (FR), respectively. Paclitaxel (PTX)-loaded FA-Pull-LA nanoparticles (NPs) with satisfactory size, polydispersity index (PDI), and zeta potential exhibited much faster PTX release in the presence of 10mM glutathione (GSH) rather than physiological conditions. In vitro cellular assays confirmed the dual targetability and endosomal accumulation of FA-Pull-LA NPs. In SMMC-7721 tumor-bearing mice, FA-Pull-LA-PTX CLNPs showed the strongest anti-tumor efficiency as well as the lowest toxicity among all three groups. Conclusively, the present study implied that reversibly crosslinked FA-Pull-LA NPs with dual-targeting capacity provided a stable and intelligent platform for efficient liver cancer therapy, which should be further studied for a wide range of anti-cancer applications.
AuthorsLiping Huang, Birendra Chaurasiya, Dawei Wu, Huimin Wang, Yunai Du, Jiasheng Tu, Thomas J Webster, Chunmeng Sun
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 14 Issue 3 Pg. 1005-1017 (04 2018) ISSN: 1549-9642 [Electronic] United States
PMID29409820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Asialoglycoprotein Receptor
  • Folate Receptor 1
  • Glucans
  • pullulan
  • Folic Acid
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology)
  • Asialoglycoprotein Receptor (metabolism)
  • Drug Delivery Systems
  • Folate Receptor 1 (metabolism)
  • Folic Acid (chemistry)
  • Glucans (chemistry)
  • Humans
  • Liver Neoplasms (drug therapy, metabolism, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles (administration & dosage, chemistry)
  • Paclitaxel (administration & dosage, chemistry, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

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