Recognition-mediated activation of therapeutic gold nanoparticles inside living cells.
Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host-guest system featuring diaminohexane-terminated gold nanoparticles (AuNP-NH(2)) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP-NH(2) through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP-NH(2) was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP-NH(2). This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.
Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, USA.
Chaekyu
C
Kim
Sarit S
SS
Agasti
Zhengjiang
Z
Zhu
Lyle
L
Isaacs
Vincent M
VM
Rotello
D045744:Cell Line, Tumor; D002470:Cell Survival; D006046:Gold / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties
D006046:Gold