ArticleBMC biotechnology2024
A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861.
Article in BMC biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 2 citations in OpenAlex.
- Improving Cytotoxicity of Saporin with Saponin SO1406 Isolated from the Roots of Saponaria Officinalis.Biomedicines · 2026Article
- The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides.Biology of the cell · 2025Review
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Authors and funding
6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatment with tumor-targeted toxins attempts to overcome the disadvantages of conventional cancer therapies by directing a drug's cytotoxic effect specifically towards cancer cells. However, success with targeted toxins has been hampered as the constructs commonly remain bound to the outside of the cell or, after receptor-mediated endocytosis, are either transported back to the cell surface or undergo degradation in lysosomes. Hence, solutions to ensure endosomal escape are an urgent need in treatment with targeted toxins. In this work, a molecular adapter that consists of a cell penetrating peptide and two cleavable peptides was inserted into a targeted toxin between the ribosome-inactivating protein dianthin and the epidermal growth factor. Applying cell viability assays, this study examined whether the addition of the adapter further augments the endosomal escape enhancement of the glycosylated triterpenoid SO1861, which has shown up to more than 1000-fold enhancement in the past.
resultsIntroducing the peptide adapter into the targeted toxin led to an about 12-fold enhancement in the cytotoxicity on target cells while SO1861 caused a 430-fold increase. However, the combination of adapter and glycosylated triterpenoid resulted in a more than 4300-fold enhancement and in addition to a 51-fold gain in specificity.
conclusionsOur results demonstrated that the cleavable peptide augments the endosomal escape mediated by glycosylated triterpenoids while maintaining specificity. Thus, the adapter is a promising addition to glycosylated triterpenoids to further increase the efficacy and therapeutic window of targeted toxins.
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