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Updated: Jul 10, 2026
Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Design of a tumor-homing cell-penetrating peptide
Helena Myrberg1, Lianglin Zhang, Maarja Mäe
1Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 21A, SE-106 91 Stockholm, Sweden. helenam@neurochem.su.se
Abstract:
Chemotherapy is often limited by toxicity to normal cells. Therefore, an ideal anticancer drug should discriminate between normal tissue and tumors. This would require a target receptor molecule mostly present in tumors. The cyclic peptide cCPGPEGAGC (PEGA) is a homing peptide that has previously been shown to accumulate in breast tumor tissue in mice. PEGA peptide does not cross the plasma membrane per se; however, when attached to the cell-penetrating peptide pVEC, the conjugate is taken up by different breast cancer cells in vitro. Additionally, the homing capacity of the PEGA- pVEC is conserved in vivo, where the conjugate mainly accumulates in blood vessels in breast tumor tissue and, consequently is taken up. Furthermore, we show that the efficacy of the anticancer drug, chlorambucil, is increased more than 4 times when the drug is conjugated to the PEGA- pVEC chimeric peptide. These data demonstrate that combining a homing sequence with a cell-penetrating sequence yields a peptide that combines the desirable properties of the parent peptides. Such peptides may be useful in diagnostics and delivery of therapeutic agents to an intracellular location in a specific tumor target tissue.
Insights
Researchers developed a novel peptide conjugate for targeted cancer therapy. This peptide delivers anticancer drugs directly to tumor cells, enhancing efficacy and reducing toxicity for improved breast cancer treatment.
Area of Science:
- Oncology
- Biotechnology
- Drug Delivery
Background:
- Chemotherapy's efficacy is limited by toxicity to normal cells, necessitating targeted drug delivery.
- A key challenge in cancer treatment is developing drugs that specifically target tumor cells while sparing healthy tissues.
- The cyclic peptide cCPGPEGAGC (PEGA) shows selective accumulation in breast tumor tissue.
Purpose of the Study:
- To develop a targeted drug delivery system for anticancer agents.
- To enhance the efficacy of chemotherapy by improving tumor cell uptake.
- To create a peptide conjugate that combines homing and cell-penetrating properties for cancer therapy.
Main Methods:
- Conjugation of the homing peptide PEGA with the cell-penetrating peptide pVEC to create a chimeric peptide.
- In vitro studies to assess the uptake of the PEGA-pVEC conjugate by breast cancer cells.
- In vivo studies to evaluate the homing capacity and tumor accumulation of the conjugate.
- Conjugation of the anticancer drug chlorambucil to the PEGA-pVEC peptide and assessment of its efficacy.
Main Results:
- The PEGA-pVEC conjugate demonstrated uptake by breast cancer cells in vitro.
- In vivo, the PEGA-pVEC conjugate showed accumulation in breast tumor vasculature and subsequent uptake.
- Conjugating chlorambucil to the PEGA-pVEC peptide resulted in a more than four-fold increase in anticancer drug efficacy.
- The chimeric peptide successfully combined the homing and cell-penetrating functionalities of its parent peptides.
Conclusions:
- The PEGA-pVEC chimeric peptide effectively targets breast tumor tissue and facilitates intracellular drug delivery.
- Drug conjugation to the PEGA-pVEC peptide significantly enhances therapeutic efficacy.
- This targeted delivery approach holds promise for improving cancer treatment outcomes by increasing drug potency and reducing systemic toxicity.
- The developed peptide conjugate system is a promising platform for future cancer diagnostics and therapeutics.
