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Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies
Published on: February 17, 2023
Smart chemistry for traceless release of anticancer therapeutics
Céline Jasmin Prange1, Xile Hu2, Li Tang3
1Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland; Institute of Chemical Sciences and Engineering, EPFL, Lausanne, CH-1015, Switzerland.
Abstract:
In the design of delivery strategies for anticancer therapeutics, the controlled release of intact cargo at the destined tumor and metastasis locations is of particular importance. To this end, stimuli-responsive chemical linkers have been extensively investigated owing to their ability to respond to tumor-specific physiological stimuli, such as lowered pH, altered redox conditions, increased radical oxygen species and pathological enzymatic activities. To prevent premature action and off-target effects, anticancer therapeutics are chemically modified to be transiently inactivated, a strategy known as prodrug development. Prodrugs are reactivated upon stimuli-dependent release at the sites of interest. As most drugs and therapeutic proteins have the optimal activity when released from carriers in their native and original forms, traceless release mechanisms are increasingly investigated. In this review, we summarize the chemical toolkit for developing innovative traceless prodrug strategies for stimuli-responsive drug delivery and discuss the applications of these chemical modifications in anticancer treatment including cancer immunotherapy.
Insights
This review explores stimuli-responsive prodrug strategies for targeted anticancer drug delivery. It highlights chemical linkers that release intact therapeutics specifically at tumor sites, minimizing side effects.
Area of Science:
- Biomedical Engineering
- Medicinal Chemistry
- Oncology
Background:
- Controlled release of intact anticancer therapeutics to tumor sites is crucial for efficacy.
- Stimuli-responsive linkers exploit tumor microenvironment characteristics (pH, redox, enzymes) for targeted drug activation.
- Prodrug strategies transiently inactivate drugs, reactivating them upon release at the intended site.
Purpose of the Study:
- To review the chemical strategies for developing innovative prodrugs for stimuli-responsive drug delivery.
- To discuss the application of these prodrug strategies in anticancer treatment, including immunotherapy.
Main Methods:
- Summarization of chemical linkers and prodrug design principles.
- Review of stimuli-responsive mechanisms triggered by tumor-specific conditions.
- Analysis of traceless release mechanisms for maintaining drug integrity.
Main Results:
- A comprehensive overview of the chemical toolkit for stimuli-responsive prodrug development is presented.
- The importance of traceless release for preserving the native form and activity of therapeutic agents is emphasized.
- Applications in anticancer therapy, including immunotherapy, are discussed.
Conclusions:
- Innovative prodrug strategies utilizing stimuli-responsive and traceless release mechanisms are vital for effective anticancer drug delivery.
- These approaches enhance therapeutic efficacy by ensuring controlled release of intact drugs at tumor and metastasis locations.
- Further development in this area holds significant promise for advancing cancer treatment and immunotherapy.
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