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Peptide-based delivery vectors with pre-defined geometrical locks.

Ruchika Goyal¹, Gaurav Jerath¹, Aneesh Chandrasekharan²

¹Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati Guwahati-781039 Assam India vibin@iitg.ac.in.

RSC Medicinal Chemistry

|June 7, 2021

Summary

Researchers designed novel peptide vectors for targeted delivery by controlling their shape and charge. These peptides show selective cell uptake and enhance drug delivery, improving cancer treatment efficacy.

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Area of Science:

Biotechnology
Molecular Biology
Drug Delivery Systems

Background:

Targeted delivery vectors are crucial for enhancing therapeutic efficacy and reducing side effects.
Peptide-based vectors offer advantages in specificity and biocompatibility.
Tumor homing peptides (THPs) are being explored for cancer targeting.

Purpose of the Study:

To design and develop peptide-based targeted delivery vectors with controlled topology and electrostatic properties.
To achieve specific and selective cellular targeting for enhanced drug delivery.
To investigate the potential of these peptides in delivering chemotherapeutic agents like methotrexate.

Main Methods:

Utilized side-chain induced geometric restrictions to lock peptide conformation, specifically RGD/NGR motifs.
Incorporated d-proline mutations and syndiotactic amphipathic segments for cellular penetration.
Synthesized and characterized designed peptides, followed by in vitro testing on various cancer and non-cancer cell lines using flow cytometry and confocal microscopy.

Main Results:

Demonstrated differential cellular uptake of designed peptides across different cell lines, attributed to their unique electrostatic fingerprints.
Confirmed retention of peptide activity after serum pre-treatment, indicating stability in biological environments.
Peptide-methotrexate (MTX) conjugates showed enhanced apoptotic cell death in MTX-resistant breast cancer cells compared to free MTX, suggesting improved bioavailability.

Conclusions:

The study successfully designed peptide vectors with tunable specificity and cellular targeting capabilities.
The developed peptide design platform offers a promising approach for creating effective targeted drug delivery systems.
These peptide-drug conjugates hold potential for overcoming drug resistance and improving cancer therapy outcomes.