Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo

Abstract

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF 2 nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.

Clip Chemistry: Diverse (Bio)(macro)molecular and Material Function through Breaking Covalent Bonds

“…As alluded to above, the limited tissue penetration of light is often a hindrance to photoinduced clip reactions in vivo. Small-molecule reagent-induced clip reactions can overcome this issue but require creative approaches to control reactivity and selectivity. − For example, Finn and co-workers have demonstrated how oxanorbornadiene derivatives, upon conjugate additions of thiols, undergo retro Diels–Alder clip reactions with tunable time scales on the orders of hours to weeks. , Additionally, while the inverse electron-demand Diels–Alder cycloaddition of tetrazines with strained alkenes has become perhaps the most promising class of click reactions for therapeutic applications, modified variants of this system enable arguably the “cream of the crop” of small-molecule triggered clip reactions (Figure ). By diverting key intermediates formed in the forward click reaction, clip reactions between tetrazines and trans -cyclooctenes, vinyl ethers, − or oxa-benzonorbornadienes have been deployed for the rapid release of payload molecules.…”

Ambient-Efficient Hydrophobic Hydration-Shell Structure for Lysosome-Tolerable Upconversion Nanoparticles with Enhanced Biosafety and Simultaneous Versatility

“…UCNP disintegration due to intrinsic solubility equilibrium leads to not only hazardous in vivo leakage of RE ions, intracellular phosphate complexation with RE ions, damage to the lysosomal membrane, and proinflammatory effects but also UCL decay . UCNP disintegration/cell dark toxicity has also been reported elsewhere. , Recently, Liu and co-workers reported the rapid disintegration of popular UCNP building units of metal fluoride nanostructures (e.g., NaYF 4 @CaF 2 and NaYF 4 ) . To prevent the disintegration of UCNPs, researchers have proposed UCNP anti-disintegration strategies such as anchoring surface ligands with strong coordination capacity or adding configurational F – to aqueous dispersions of UCNPs. ,, Tetraphosphate-coated UCNPs can tolerate phagolysosomal simulated fluid (PSF, pH 4.5) but still disintegrate obviously in lysosomes .…”

“…1,16 Recently, Liu and co-workers reported the rapid disintegration of popular UCNP building units of metal fluoride nanostructures (e.g., NaYF 4 @CaF 2 and NaYF 4 ). 17 UCNPs. 13,15,18 Tetraphosphate-coated UCNPs can tolerate phagolysosomal simulated fluid (PSF, pH 4.5) but still disintegrate obviously in lysosomes.…”

Cation-Ligand Complexation Mediates the Temporal Evolution of Colloidal Fluoride Nanocrystals through Transient Aggregation

“…Because of their unique physical, chemical, and electronic properties, colloidal inorganic fluoride nanocrystals (NCs), namely, nanofluorides, have found applications over the last two decades as functional materials in a variety of fields, including photonics, bioimaging, biomedicine, sensing, catalysis, and more. A case in point are colloidal CaF 2 , which were developed for upconversion fluorescence, time-resolved luminescent, antifungal coating, in vivo magnetic resonance imaging (MRI), − prodrug activation, photodynamic therapy, remineralization of dental caries, and in situ NMR studies . In all these studies, the colloidal characteristics of the synthetic CaF 2 NCs are of paramount importance to their desired properties and function.…”