148579-93-5Relevant articles and documents
Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells
Herceg,Adriouach,Janikowska,Allémann,Lange,Babi?
, p. 372 - 380 (2018)
Treatment of cancer cells by clinically approved hexyl ester of 5-aminolevulinic acid (ALA-Hex) induces accumulation of fluorescent porphyrins in tumors. This allows fluorescence photodiagnosis (PD) of bladder cancer by blue light illumination. However, PD of other cancers is hampered by acute toxicity of the compound limiting its use to local applications. We have designed and synthesized a new prodrug of ALA-Hex that tackles the stability-activity paradox of amino-modified 5-ALA prodrugs. The glucuronide prodrug Glu-ALA-Hex demonstrates excellent stability under physiological conditions and activation in the presence of the target enzyme. β-glucuronidase-triggered release of 5-ALA is programmed to yield fluorescence in tumor environment with elevated β-glucuronidase activity, a characteristic of many solid tumors. Glu-ALA-Hex produces similar levels of fluorescence as ALA-Hex in breast cancer MCF7 cells in vitro but with much lower non-specific cell toxicity.
Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release
Calatrava-Pérez, Elena,Elmes, Robert B. P.,Gunnlaugsson, Thorfinnur,Lynch, Dylan M.,Marchetti, Luke A.,McManus, Gavin J.,Scanlan, Eoin M.,Williams, D. Clive
, (2021/12/09)
Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzyma
Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates
Anselmi, Michele,Borbély, Adina,Figueras, Eduard,Michalek, Carmela,Kemker, Isabell,Gentilucci, Luca,Sewald, Norbert
supporting information, p. 1015 - 1022 (2020/12/11)
Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor-selective treatment options. A hydrophilic β-glucuronidase-cleavable linker was used to connect the highly potent antimitotic agent cryptophycin-55 glycinate with the αvβ3 integrin ligand c(RGDfK). Incorporation of the self-immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug-release studies and cytotoxicity assays demonstrated the potential of this small molecule–drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs.
BIO-ACTIVATED REPORTERS TO VISUALIZE, IN REAL TIME, SPECIFIC GENE THERAPY PRODUCTS
-
Paragraph 0022; 0139, (2021/02/05)
Provided herein are MRI contrast agents that are conditionally activated by an enzyme from a reporter gene coupled to a gene of interest. In some embodiments, provided herein is a platform where a substrate (blocking access of water to a Gd(III) ion) is r