β-Galactosidase-activated theranostic for hepatic carcinoma therapy and imaging

Maiti, Mrinmoy; Kikuchi, Kai; Athul, K. K.; Kaur, Amandeep; Bhuniya, Sankarprasad

doi:10.1039/d2cc01825j

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…Accordingly, a bioreversible linkage (e.g., the GSH trigger, i.e., discussed in this review) attached to the self‐immolating spacer can be utilized to facilitate the connection of a broad range of tertiary and heteroaryl amine‐containing drugs for prodrug‐based therapeutic interventions. Moreover, for the vast majority of drugs lacking intrinsic fluorescent properties, the incorporation of self‐immolating spacers that exhibit fluorescence upon activation represents a widely employed strategy 82,235–239 . Nonetheless, a significant challenge arises from the suboptimal performance of these commonly used self‐immolating spacer groups in vivo imaging, owing to their emission wavelengths typically falling below 500 nm.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, for the vast majority of drugs lacking intrinsic fluorescent properties, the incorporation of self-immolating spacers that exhibit fluorescence upon activation represents a widely employed strategy. 82,[235][236][237][238][239] Nonetheless, a significant challenge arises from the suboptimal performance of these commonly used self-immolating spacer groups in vivo imaging, owing to their emission wavelengths typically falling below 500 nm. Hence, the quest for self-immolating moieties emitting within the NIR region becomes particularly imperative.…”

Section: F I G R E 21mentioning

confidence: 99%

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Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives

Zhao,

Li,

et al. 2023

Medicinal Research Reviews

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The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH‐triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer‐based and organic–inorganic nanomaterial constructs. Although the GSH‐triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple‐targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH‐triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH‐triggered prodrugs in the future. By assessing the pros and cons of current GSH‐triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH‐triggered prodrugs.

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Section: Discussionmentioning

confidence: 99%

Section: F I G R E 21mentioning

confidence: 99%

Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives

Zhao,

Li,

et al. 2023

Medicinal Research Reviews

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“…Different works have focused on β-galactosidase-activated theranostics using DOX as a self-reporting agent. Among them, Maiti et al [ 69 ] have developed a β-galactosidase-activated theranostic based on gemcitabine called GAL-CGem ( Scheme 10 ). GAL-CGem consists of a galactose-substituted coumarin scaffold linked to gemcitabine, an anti-cancer drug.…”

Section: Galactose For Theranosticsmentioning

confidence: 99%

Galactose: A Versatile Vector Unveiling the Potentials in Drug Delivery, Diagnostics, and Theranostics

Battisegola,

Billi,

Molaro

et al. 2024

Pharmaceuticals

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D-galactose, a simple natural compound, has been investigated as a powerful scaffold for drug delivery, diagnostics, and theranostics due to its distinctive properties and interactions with specific cell receptors. In the field of drug delivery, galactose functions as a ligand to selectively target cells expressing galactose receptors, such as hepatocytes, macrophages, and specific cancer cells. The direct attachment of galactose to the main drug or to drug-loaded nanoparticles or liposomes enhances cellular uptake, thereby improving drug delivery to the intended target cells. Galactose has also been found to be useful in diagnostics. Specifically, diagnostic tests based on galactose, such as the galactose elimination capacity test, are utilized to evaluate liver function and assess liver disease as well as hepatic functional reserve. Additionally, galactose-based theranostic agents can be designed by combining drug delivery and diagnostic capabilities. This review is an update of our previous review concerning the broad spectrum of possibilities for exploiting D-galactose as a vector for prodrug design and the synthetic strategies that allow its realization, jointly in diagnostics and theranostics, to highlight the versatility of this interesting vector.

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“…37). 265 This substance was comprised of gemcitabine as an anticancer agent and β-galactoside with the two moieties being conjugated at the 8-C and 7-O positions of a coumarin fluorophore, respectively. Addition of β-galactosidase to 85 promoted hydrolytic cleavage of β-galactoside and release of gemcitabine and free coumarin which emitted intense fluorescence at 450 nm ( λ ex = 400 nm).…”

Section: Prodrugsmentioning

confidence: 99%

Glycosidase-targeting small molecules for biological and therapeutic applications

Kim,

Li,

Choi

et al. 2023

Chem. Soc. Rev.

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β-Galactosidase-activated theranostic for hepatic carcinoma therapy and imaging

Abstract: A β-galactosidase activatable fluorescent turn-on theranostic Gal-CGem exhibits gemcitabine release specifically to the β-galactosidase overexpressed hepatic carcinoma cells. The cytotoxicity of Gal-CGem in cancer cells is achieved through apoptotic cell...

Cited by 12 publications

References 22 publications

Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives

Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives

Galactose: A Versatile Vector Unveiling the Potentials in Drug Delivery, Diagnostics, and Theranostics

Glycosidase-targeting small molecules for biological and therapeutic applications

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