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Abstract The rational design of materials with cell‐selective membrane activity is an effective strategy for the development of targeted molecular imaging and therapy. Here we report a new class of cationic multidomain peptides (MDPs) that can undergo enzyme‐mediated molecular transformation followed by supramolecular assembly to form nanofibers in which cationic clusters are presented on a rigid β‐sheet backbone. This structural transformation, which is induced by cells overexpressing the specific enzymes, led to a shift in the membrane perturbation potential of the MDPs, and consequently enhanced cell uptake and drug delivery efficacy. We envision the directed self‐assembly based on modularly designed MDPs as a highly promising approach to generate dynamic supramolecular nanomaterials with emerging membrane activity for a range of disease targeted molecular imaging and therapy applications.
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Light‐Triggered Protease‐Mediated Release of Actin‐Bound Cargo from Synthetic Cells
Abstract Synthetic cells offer a versatile platform for addressing biomedical and environmental challenges, due to their modular design and capability to mimic cellular processes such as biosensing, intercellular communication, and metabolism. Constructing synthetic cells capable of stimuli‐responsive secretion is vital for applications in targeted drug delivery and biosensor development. Previous attempts at engineering secretion for synthetic cells have been confined to non‐specific cargo release via membrane pores, limiting the spatiotemporal precision and specificity necessary for selective secretion. Here, a protein‐based platform termed TEV Protease‐mediated Releasable Actin‐binding Protein (TRAP) is designed and constructed for selective, rapid, and triggerable secretion in synthetic cells. TRAP is designed to bind tightly to reconstituted actin networks and is proteolytically released from bound actin, followed by secretion via cell‐penetrating peptide membrane translocation. TRAP's efficacy in facilitating light‐activated secretion of both fluorescent and luminescent proteins is demonstrated. By equipping synthetic cells with a controlled secretion mechanism, TRAP paves the way for the development of stimuli‐responsive biomaterials, versatile synthetic cell‐based biosensing systems, and therapeutic applications through the integration of synthetic cells with living cells for targeted delivery of protein therapeutics.
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- Award ID(s):
- 2201236
- PAR ID:
- 10640327
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Biology
- Volume:
- 9
- Issue:
- 5
- ISSN:
- 2701-0198
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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