Metal-free bioorthogonal click chemistry in cancer theranostics

Abstract

In this Review, recent progress in cancer theranostics on the basis of metal-free bioorthogonal click chemistry is depicted in detail and future prospects in this emerging field are emphasized.

A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy

“…As an alternative to conventional chemotherapy, prodrug approaches are considered a promising solution to the drug side effects caused by off-target effect. The CuAAC reaction as one of the representative bioorthogonal reactions, [1][2][3][4][5][6][7][8][9][10][11] has now become a powerful tool for prodrug activation or drug synthesis in situ. [12][13][14][15][16] However, the intrinsic toxicity of Cu(I) to organisms hampered its application in biological systems.…”

The Construction of Cucurbit[7]uril-Based Supramolecular Nanomedicine for Glioma Therapy

“…Because most of the chemotherapeutic drugs are hydrophobic molecules, they have poor solubility and stability in physiological environments, thus leading to the limited therapeutic effect ( Zhou et al, 2017 ). Nanomedicines are receiving increasing attentions over the past decades because of their ability to promote the pharmacokinetics of drugs, enhance the therapeutic efficacy, and decrease the side effects of drugs ( Janib et al, 2010 ; Lee et al, 2012 ; Oun et al, 2018 ; Xue et al, 2018 ; Wu et al, 2022 ). Incorporation of traditional chemotherapeutic drugs into nanomedicine is an effective method to overcome the limitations of conventional chemotherapy.…”

A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy

“…Chemotherapy is widely used as the most traditional treatment in cancer, − whereas systemic administration of classic anticancer drugs is often detrimental to normal cells due to the limited target selectivity and random biodistribution. − To minimize off-target toxicity, selective activating drugs in target cells is a prospective approach. ,− Of special note, the booming bioorthogonal chemistry is an appealing candidate which can activate an inert prodrug into a cytotoxic species at the desired location. ,,,− Several types of bioorthogonal reactions have been developed as a powerful tool for prodrug activation. − Very recently, fluoride-mediated desilylation reported by Liu and co-workers has emerged as a burgeoning bioorthogonal system, in which organotrifluoroborate could catalyze the cleavage of silyl ether to activate prodrug or client protein in vivo specifically and efficiently . Furthermore, CaF 2 nanocrystals and cationic micelles have been designed as catalysts to trigger the desilylation chemistry in vivo . , Generally, this kind of bioorthogonal reaction exhibits fast kinetics and high bioorthogonality. ,,, However, the existing fluoride catalysts are short of cell selectivity, which may result in inevitable off-target effects for in vivo application.…”