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

2 Citations (Scopus)

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
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Quinic Acid
Selectins
Drug delivery
Nanoparticles
Tumors
Paclitaxel
Acids
Pharmaceutical Preparations
Permeability
Neoplasms
Endothelium
Polyethylene glycols
Bearings (structural)
Drug Carriers
P-Selectin
E-Selectin
Endothelial cells
Human Umbilical Vein Endothelial Cells
Animals
Animal Models

Keywords

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

ASJC Scopus subject areas

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

Cite this

Xu, J., Lee, S. S. Y., Seo, H., Pang, L., Jun, Y., Zhang, R. Y., ... Yeo, Y. (Accepted/In press). Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins. Small, [1803601]. https://doi.org/10.1002/smll.201803601

Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins. / Xu, Jun; Lee, Steve Seung Young; Seo, Howon; Pang, Liang; Jun, Yearin; Zhang, Ruo Yu; Zhang, Zhong-Yin; Kim, Pilhan; Lee, Wooin; Kron, Stephen J.; Yeo, Yoon.

In: Small, 01.01.2018.

Research output: Contribution to journalArticle

Xu, Jun ; Lee, Steve Seung Young ; Seo, Howon ; Pang, Liang ; Jun, Yearin ; Zhang, Ruo Yu ; Zhang, Zhong-Yin ; Kim, Pilhan ; Lee, Wooin ; Kron, Stephen J. ; Yeo, Yoon. / Quinic Acid-Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins. In: Small. 2018.
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