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Enzyme-instructed self-assembly: a multistep process for potential cancer therapy
1Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, United States.
Abstract:
The central dogma of the action of current anticancer drugs is that the drug tightly binds to its molecular target for inhibition. The reliance on tight ligand-receptor binding, however, is also the major root of drug resistance in cancer therapy. In this article, we highlight enzyme-instructed self-assembly (EISA)-the integration of enzymatic transformation and molecular self-assembly-as a multistep process for the development of cancer therapy. Using apoptosis as an example, we illustrate that the combination of enzymatic transformation and self-assembly, in fact, is an inherent feature of apoptosis. After the introduction of EISA of small molecules in the context of supramolecular hydrogelation, we describe several key studies to underscore the promises of EISA for developing cancer therapy. Particularly, we will highlight that EISA allows one to develop approaches to target "undruggable" targets or "untargetable" features of cancer cells and provides the opportunity for simultaneously interacting with multiple targets. We envision that EISA, used separately or in combination with current anticancer therapeutics, will ultimately lead to a paradigm shift for developing anticancer medicine that inhibit multiple hallmark capabilities of cancer.
Insights
Enzyme-instructed self-assembly (EISA) offers a novel approach to cancer therapy by overcoming drug resistance. This method integrates enzymatic action with molecular self-assembly for targeted cancer treatment.
Area of Science:
- Biochemistry
- Materials Science
- Oncology
Background:
- Current anticancer drugs rely on tight binding to molecular targets, a mechanism often leading to drug resistance.
- Drug resistance remains a significant challenge in effective cancer therapy.
Purpose of the Study:
- To highlight enzyme-instructed self-assembly (EISA) as a novel multistep process for developing advanced cancer therapies.
- To demonstrate EISA's potential in overcoming limitations of current drug-receptor binding strategies.
Main Methods:
- Integration of enzymatic transformation with molecular self-assembly principles.
- Application of EISA in supramolecular hydrogelation for therapeutic delivery.
- Utilizing apoptosis as a model to illustrate EISA's mechanism.
Main Results:
- EISA leverages the inherent self-assembly features observed in biological processes like apoptosis.
- EISA enables targeting previously "undruggable" cancer targets and "untargetable" cellular features.
- EISA facilitates simultaneous interaction with multiple cancer targets.
Conclusions:
- Enzyme-instructed self-assembly presents a promising strategy for developing next-generation cancer therapeutics.
- EISA has the potential to shift the paradigm in cancer medicine by inhibiting multiple cancer hallmarks.
- EISA can be used independently or in combination with existing anticancer treatments for enhanced efficacy.
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