Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.


Duan D(1), Dong H(2), Tu Z(1), Wang C(1), Fu Q(1), Chen J(1), Zhong H(1), Du P(2), Sun LD(2), Liu Z(1)(3)(4).
Author information:
(1)Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
(2)Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, PKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
(3)Beijing Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China.
(4)Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.


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 CaF2 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.