The combination of cell-penetrating peptide (CPPs)-based delivery systems with therapeutic drugs has renewed attention in this field. It utilizes specific short peptide sequences to efficiently penetrate cell membranes, precisely delivering drugs, genes, and other bioactive molecules into the cell interior. This system offers advantages such as good biocompatibility, high cellular uptake efficiency, and the ability to target specific cell types, and is widely applied in fields like cancer therapy and gene therapy.
Cell-penetrating peptides (CPPs) are short peptides, typically composed of 5 to 30 amino acids, characterized by their cationic or amphipathic nature, enabling them to traverse cell membranes. CPPs can transport various cargoes, including nanocarriers, drugs, and nucleic acids, into cells, thereby enhancing the intracellular uptake efficiency of therapeutic molecules and facilitating their therapeutic effects. In recent years, CPP-based drug delivery systems have achieved significant progress in clinical trials, primarily in the fields of cancer, cardiovascular disease, and imaging.
Fig. 1 Different mechanisms of CPPs interacting with the membrane. (Ouyang J, et al., 2022)
Cell-penetrating peptides (CPPs) are increasingly important in drug delivery and disease diagnosis due to their precise control of transmembrane transport, especially in the fields of inflammation, central nervous system, ocular, and cancer therapies. Basic and preclinical studies have demonstrated the significant potential of CPP-based therapies. However, no CPP drugs have yet been approved by the FDA. To achieve clinical application and overcome therapeutic challenges, it is urgently necessary to design and optimize CPPs to achieve low toxicity, high efficiency, and specificity.
Table 1. CPPs-based delivery platforms in clinical phase. (Xiao W, et al., 2025)
| Name | CPPs | Cargo | Indications |
| ALRN-6924 | A cell-penetrating stapled alpha-helical peptide structure undisclosed | Palbociclib | Solid tumour |
| PsorBan | R7 | Cyclosporin A | Psoriasis |
| AZX100 | PTD4 | HSP20 phosphopeptide | Scar prevention / reduction |
| RT001 | MTSsss | Botulinum toxin A | Lateral canthal, Line, Crow's feet, Facial wrinkles |
| AEM-28 | A high-affinity lipid-associating peptide (DWLKAFYDKVAEKLKEAF) | An arginine-rich apo E receptor binding domain (residues 141-150 LRKLRKRL-LR) | Type II hyperlipoproteinemia |
| PEP-010 | NA | Interfering peptide | Metastatic solid tumor cancer |
Leveraging its advanced computational technologies and profound professional expertise, CD ComputaBio offers CPP design services to advance the development of CPPs-based drug delivery systems.
Cell-Penetrating Peptides Screening
CD ComputaBio offers cell-penetrating peptide screening services, utilizing machine learning and other algorithms to rapidly screen peptide sequences with high cell penetration capabilities, accelerating the development of drug delivery systems.
Cell-Penetrating Peptide Design
Based on target cell characteristics, designing cell-penetrating peptides by combining amino acid sequences, utilizing computational tools for predicting their membrane translocation ability, optimizing hydrophobicity and charge distribution to meet drug delivery needs.
Cell-Penetrating Peptide Optimization
By employing methods such as molecular dynamics simulations, adjusting the amino acid composition and sequence of cell-penetrating peptides, optimizing their structure for enhancing cell penetration efficiency, increasing stability, and reducing immunogenicity.
Simulating the atomic-level interactions of CPPs with membranes, providing detailed dynamic information of the membrane translocation process, but being limited by simulation timescales and sampling efficiency.
By applying external forces or introducing biasing potentials, accelerating the CPP translocation process and improving sampling efficiency, being used for calculating free energies and studying complex pathways.
Simplifying atoms into coarse-grained units, reducing computational costs, and being suitable for studying large-scale structural changes and dynamic behavior of CPPs with membranes.
Extracting long-timescale dynamic information from short trajectories, analyzing CPP translocation pathways and rates, and determining key states and transition probabilities.
With a professional team, advanced computational platforms, and extensive industry experience, CD ComputaBio is able to provide you with high-quality, customized solutions. Please feel free to contact us anytime. We look forward to working with you hand-in-hand to create a new future for drug delivery.
References:
CD ComputaBio offers computation-driven peptide design services to research institutions, pharmaceutical, and biotechnology companies.
