Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins

Jun Xu, Steve Seung Young Lee, Howon Seo, Liang Pang, Yearin Jun, Ruo Yu Zhang, Zhong Yin Zhang, Pilhan Kim, Wooin Lee, Stephen J. Kron, Yoon Yeo

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Current nanoparticle (NP) drug carriers mostly depend on the enhanced permeability and retention (EPR) effect for selective drug delivery to solid tumors. However, in the absence of a persistent EPR effect, the peritumoral endothelium can function as an access barrier to tumors and negatively affect the effectiveness of NPs. In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic-co-glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA-decorated NPs (QA-NP) interact with human umbilical vein endothelial cells expressing E-/P-selectins and induce transient increase in endothelial permeability to translocate across the layer. QA-NP reach selectin-upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol-decorated NPs (PEG-NP). PTX-loaded QA-NP show greater anticancer efficacy than Taxol or PTX-loaded PEG-NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX-loaded QA-NP for two weeks results in complete tumor remission in 40–60% of MDA-MB-231 tumor-bearing mice, while those receiving control treatments succumb to death. QA-NP can exploit the interaction with selectin-expressing peritumoral endothelium and deliver anticancer drugs to tumors to a greater extent than the level currently possible with the EPR effect.

Original languageEnglish (US)
Article number1803601
JournalSmall
Volume14
Issue number50
DOIs
StatePublished - Dec 13 2018
Externally publishedYes

Keywords

  • drug delivery
  • polymeric nanoparticles
  • quinic acid
  • selectin
  • tumor microenvironment

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

Fingerprint Dive into the research topics of 'Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins'. Together they form a unique fingerprint.

  • Cite this

    Xu, J., Lee, S. S. Y., Seo, H., Pang, L., Jun, Y., Zhang, R. Y., Zhang, Z. Y., Kim, P., Lee, W., Kron, S. J., & Yeo, Y. (2018). Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins. Small, 14(50), [1803601]. https://doi.org/10.1002/smll.201803601