Ligand Conformation Dictates Membrane and Endosomal Trafficking of Arginine-Glycine-Aspartate (RGD)-Functionalized Mesoporous Silica Nanoparticles

TitleLigand Conformation Dictates Membrane and Endosomal Trafficking of Arginine-Glycine-Aspartate (RGD)-Functionalized Mesoporous Silica Nanoparticles
Publication TypeJournal Article
Year of Publication2012
AuthorsFang IJ, Slowing II, Wu KCW, Lin VSY, Trewyn BG
Journal TitleChemistry-A European Journal
Volume18
Pages7787-7792
Date Published06
Type of ArticleArticle
ISBN Number0947-6539
Accession NumberWOS:000305187300019
Keywordscancer-cells, CARRIERS, cell recognition, cell-adhesion molecules, CONTROLLED-RELEASE, drug-delivery, endocytosis, functionalization, integrin, mesoporous materials, metastasis, RGD, stability
Abstract

Recent breakthrough research on mesoporous silica nanoparticle (MSN) materials has illustrated their significant potential in biological applications due to their excellent drug delivery and endocytotic behavior. We set out to determine if MSN, covalently functionalized with conformation specific bioactive molecules (either linear or cyclic RGD ligands), behave towards mammalian cells in a similar manner as the free ligands. We discovered that RGD immobilized on the MSN surface did not influence the integrity of the porous matrix and improved the endocytosis efficiency of the MSN materials. Through competition experiments with free RGD ligands, we also discovered a conformation specific receptorintegrin association. The interaction between RGD immobilized on the MSN surface and integrins plays an important role in endosome trafficking, specifically dictating the kinetics of endosomal escape. Thus, covalent functionalization of biomolecules on MSN assists in the design of a system for controlling the interface with cancer cells.

URL<Go to ISI>://WOS:000305187300019http://onlinelibrary.wiley.com/store/10.1002/chem.201200023/asset/7787_ftp.pdf?v=1&t=h4q031yk&s=267ddb9cefb3f3aa686ff8cbc294d6753947620a
DOI10.1002/chem.201200023
Alternate JournalChem.-Eur. J.