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Design and In Vitro Application of Bioactive Cell-Penetrating Peptides as Effective Therapeutic Agents for Corneal
1Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, India.
Abstract:
The management of corneal injuries remains a formidable global health challenge, yet current therapeutic strategies remain supportive rather than actively regenerative, primarily because current clinical standards fail to address the delicate biological tension between rapid re-epithelialization and the risk of permanent fibrotic scarring. To address this unmet need, we report the design, applications, and mechanisms of novel collagen-derived cell-penetrating peptides that function as dual-action bioactive agents. In human corneal epithelial cells, these peptides demonstrated efficient cell-penetrating capabilities and macromolecular cargo delivery. All-atom molecular dynamics simulations revealed that these peptides interact with membrane interfaces through distinct energetic profiles, facilitating the rapid translocation. Beyond their utility as delivery vectors, the peptides exhibited intrinsic, dose-dependent wound healing activity in vitro. Mechanistic investigations revealed that this capacity is driven by targeted transcriptional modulation. Both peptides suppressed fibrotic and matrix-degradation genes while simultaneously upregulating pathways governing migration, epithelial identity, and proliferation. These results suggest that rationally engineered peptides can navigate complex microenvironments to actively enforce tissue integrity. Furthermore, they offer a promising peptide-based strategy that promotes corneal epithelial repair through an intrinsic, nonfibrotic mechanism while offering a potential platform for intracellular cargo delivery.
Insights
Novel collagen-derived peptides promote corneal healing by enhancing cell repair and regeneration. These cell-penetrating peptides deliver cargo and actively improve tissue integrity without fibrotic scarring, offering a new therapeutic approach.
Area of Science:
- Biomaterials Science
- Ophthalmology
- Regenerative Medicine
Background:
- Corneal injury management faces challenges due to the conflict between re-epithelialization and fibrotic scarring.
- Current therapies are supportive, lacking active regenerative capabilities for corneal injuries.
Purpose of the Study:
- To design and investigate novel collagen-derived cell-penetrating peptides for corneal repair.
- To evaluate the dual-action potential of these peptides in promoting non-fibrotic corneal healing and intracellular delivery.
Main Methods:
- Design and synthesis of collagen-derived cell-penetrating peptides.
- In vitro assessment of cell-penetrating capabilities and cargo delivery in human corneal epithelial cells.
- All-atom molecular dynamics simulations to understand peptide-membrane interactions.
- In vitro wound healing assays and mechanistic studies involving transcriptional modulation.
Main Results:
- Peptides demonstrated efficient cell penetration and macromolecular cargo delivery.
- Molecular dynamics simulations revealed rapid peptide translocation across membrane interfaces.
- Peptides exhibited intrinsic, dose-dependent wound healing activity, suppressing fibrotic genes and upregulating repair pathways.
- The peptides promoted corneal epithelial repair via a non-fibrotic mechanism.
Conclusions:
- Rationally engineered peptides can actively promote corneal epithelial integrity and repair.
- These peptides offer a dual-action strategy for corneal wound healing and intracellular delivery.
- The developed peptides represent a promising platform for regenerative therapies in ophthalmology.
