A novel anticancer theranostic pro-prodrug based on hypoxia and photo sequential control

Feng, Weipei; Gao, Chunyue; Liu, Wei; Ren, Huihui; Wang, Chao; Ge, Kun; Li, Shenghui; Zhou, Guoqiang; Li, Hongyan; Wang, Shuxiang; Jia, Guang; Li, Zhenhua; Zhang, Jinchao

doi:10.1039/c6cc02932a

Cited by 58 publications

(46 citation statements)

References 50 publications

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“…in compound 41 DT‐diaphorase removes a quinone propionic acid moiety, depicted in green) or by hypoxic conditions (e.g. nitroarene reduction and subsequent self‐immolation of the resulting PABE spacer in compound 42 ) …”

Section: When and Where: Linker Cleavage Promoted By External Stimulimentioning

confidence: 99%

“…Similarly, the gemcitabine payload was masked by both a coumarin precursor and a hypoxia‐sensitive nitroarene (pro‐prodrug 42 in Scheme ). Reduction of the nitro group under hypoxic conditions and UV light‐induced C=C isomerization (conversion from 43 to 44 ) resulted in drug release, whereas no in vitro anticancer activity was detected in the absence of one of the two stimuli . Besides the double‐controlled drug release, the pro‐prodrugs of this class find also application as theranostic devices.…”

Section: When and Where: Linker Cleavage Promoted By External Stimulimentioning

confidence: 99%

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Innovative Linker Strategies for Tumor‐Targeted Drug Conjugates

Corso

Pignataro

Belvisi

et al. 2019

Chemistry A European J

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The covalent conjugation of potent cytotoxic agents to either macromolecular carriers or small molecules represents a well‐known approach to increase the therapeutic index of these drugs, thus improving treatment efficacy and minimizing side effects. In general, cytotoxic activity is displayed only upon cleavage of a specific chemical bond (linker) that connects the drug to the carrier. The perfect balance between the linker stability and its selective cleavage represents the key for success in these therapeutic approaches and the chemical toolbox to reach this goal is continuously expanding. In this Review article, we highlight recent advances on the different modalities to promote the selective release of cytotoxic agents, either by exploiting specific hallmarks of the tumor microenvironment (e.g. pH, enzyme expression) or by the application of external triggers (e.g. light and bioorthogonal reactions).

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Section: When and Where: Linker Cleavage Promoted By External Stimulimentioning

confidence: 99%

Section: When and Where: Linker Cleavage Promoted By External Stimulimentioning

confidence: 99%

Innovative Linker Strategies for Tumor‐Targeted Drug Conjugates

Corso

Pignataro

Belvisi

et al. 2019

Chemistry A European J

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“…Those characteristics incite metabolic alterations that can change the pH [45, 46], miRNA and gene expression [47–51], and redox potential [52–61] of the tumor microenvironment. Table 2 shows the different types of internal stimuli present in the tumor microenvironment and the corresponding response materials to control the activation and behavior of nanostructures.…”

Section: Introductionmentioning

confidence: 99%

“…[62, 63, 67]Hypoxia and oxidative stress4-nitrobenzyl group (hypoxic trigger), o-hydroxyl E-cinnamic ester (photo-activated group), MnO (glutathione), quaternized chlormethine (H 2 O 2 )Ref. [52–61]Nucleic acid basedmolecular beaconRef. [47–51] …”

Section: Introductionmentioning

confidence: 99%

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Strategies for using nanoprobes to perceive and treat cancer activity: a review

et al. 2017

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Nanomedicine has seen a significant increase in research on stimuli-responsive activatable nanoprobes for tumor-specific delivery and diagnosis. The tumor microenvironment has particular characteristics that can be exploited to implement therapeutic strategies based on disparities between normal tissues and tumor tissues, including differences in pH, oxygenation, enzymatic expression, gene activation/inactivation, and vasculature. The nanocarriers of activatable nanoparticles maintain their structure while circulating in the body and, upon reaching the tumor site, are altered by unique tumoral stimuli, leading to the release of a drug or other agent. This review demonstrates the latest achievements in the use of internal stimuli-responsive, activatable nanoparticles with respect to unique design strategies and applications.

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