Welcome to this edition, where we dive into cutting-edge advances in peptide-based drug delivery systems (DDS) – a game-changer in enhancing therapeutic efficacy and reducing off-target effects.
Why Peptides for DDS?
Peptides (≤40 amino acids, per FDA) offer unique advantages: biocompatibility, low immunogenicity, easy synthesis, and versatile modification. Their ability to carry functional groups (carboxylic acids, hydroxyls, etc.) makes them ideal for designing DDS that control drug release, target specific tissues, and boost therapeutic concentrations at disease sites.
Key Innovations & Applications
Peptide-Drug Conjugates (PDCs)
Smaller than antibodies, PDCs penetrate tissues efficiently and target overexpressed receptors on tumor cells. Bicycle Therapeutics’ BT8009 (Phase III) leads the field, achieving a 38% objective response rate (ORR) in metastatic urothelial cancer with fewer side effects than ADCs of the same class.
PRRT: Targeted Radionuclide Therapy
Peptide Receptor Radionuclide Therapy (PRRT) uses radiolabeled peptides to home in on cancer cells. PeptiDream’s pipeline, including FXX489 (with Novartis), shows promise as a potential best-in-class treatment, with ²²⁵Ac-PD-32766 demonstrating strong anti-tumor effects in colorectal models.
Cell-Penetrating Peptides (CPPs)
CPPs breach cell membranes to deliver drugs intracellularly. PepGen’s EDO™ platform, for example, enhances oligonucleotide delivery with improved kidney safety, outperforming conventional systems.
Stimuli-Responsive Peptides
These “smart” peptides react to tumor microenvironment cues (pH, enzymes, redox signals) to release drugs precisely. Examples include pH-sensitive GALA peptides (aiding endosome escape) and enzyme-responsive systems (e.g., MMP-triggered drug release), boosting targeting accuracy.
