John Garner

PLGA-FITC and PLGA-NH2 from PolySciTech used in development of quinic-acid decorated nanoparticles for cancer delivery

Blog Post created by John Garner on Dec 4, 2018

Yeo, PLGA-QA.PNG

Due to the toxicity of most chemotherapeutic agents, there is a need to ensure the preferential localization of these compounds into the tumor site for appropriate activity. One compound, quinic acid, has presented promise for use as a targeting ligand against tumor cells. Recently, researchers at Purdue University used PLGA-NH2 (AI017) and PLGA-FITC (AV001) from PolySciTech (www.polyscitech.com) to develop and test nanoparticles for uptake to tumors. This research holds promise for improved therapies against cancer. Read more: Xu, Jun, Steve Seung‐Young Lee, Howon Seo, Liang Pang, Yearin Jun, Ruo‐Yu Zhang, Zhong‐Yin Zhang et al. "Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins." Small (2018): 1803601. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201803601

 

“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.”

 

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