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Preparation of Multifunctional Silk-Based Microcapsules Loaded with DNA Plasmids Encoding RNA Aptamers and Riboswitches
Published on: October 8, 2021
Intracellular processing of proteins mediated by biodegradable polyelectrolyte capsules
Pilar Rivera-Gil1, Stefaan De Koker, Bruno G De Geest
1Fachbereich Physik und Wissenschaftliches Zentrum für Materialwissenschaften, Philipps Universität Marburg, Renthof 7, 35037 Marburg, Germany.
Nano Letters
|October 29, 2009
Summary
Biodegradable capsules deliver prodrugs into cells, where intracellular enzymes activate them into fluorescent drugs. This targeted activation ensures therapeutic molecules are only released within the body, not outside.
Area of Science:
- Biomaterials Science
- Cell Biology
- Drug Delivery
Background:
- Layer-by-layer assembly enables the creation of multilayer polyelectrolyte capsules.
- Biodegradable polyelectrolytes offer potential for controlled drug release systems.
- Prodrug strategies require specific activation mechanisms for therapeutic efficacy.
Purpose of the Study:
- To develop and evaluate biodegradable capsules for intracellular prodrug activation.
- To demonstrate the conversion of nonactive prodrugs into active drugs within living cells.
- To investigate the role of intracellular proteases in capsule degradation and cargo activation.
Main Methods:
- Fabrication of multilayer polyelectrolyte capsules using layer-by-layer assembly.
- Encapsulation of a model prodrug: a self-quenched, fluorescence-labeled protein.
- Incubation of capsules with living cells to assess cellular uptake and intracellular processing.
- Analysis of capsule wall degradation and cargo activation by intracellular proteases.
Main Results:
- Biodegradable capsules were successfully synthesized and loaded with a model prodrug.
- Cellular uptake of capsules was confirmed, followed by active degradation of capsule walls by intracellular proteases.
- Enzymatic fragmentation of the encapsulated protein revoked self-quenching, leading to fluorescence signal generation.
- Prodrug activation occurred specifically within cells, demonstrating enzyme-dependent intracellular conversion.
Conclusions:
- Biodegradable polyelectrolyte capsules facilitate targeted intracellular activation of prodrugs.
- Intracellular proteases play a crucial role in capsule degradation and subsequent drug activation.
- This approach enables site-specific drug activation, enhancing therapeutic potential and minimizing off-target effects.
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