Thermally Targeted p50 Peptide Inhibits Proliferation and Induces Apoptosis of Breast Cancer Cell Lines

• Published in: Macromolecular bioscience Vol. 20; no. 10; pp. e2000170 - n/a
• Main Authors: Thomas, Emily, Dragojevic, Sonja, Price, Amira, Raucher, Drazen
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-10-2020
• Subjects: Apoptosis; Biopolymers; Breast cancer; Cancer; Cell death; cell penetrating peptide; Cell proliferation; Cell survival; drug delivery; Elastin; elastin‐like polypeptide; Localization; Macromolecules; Metastases; NF-κB protein; p50; Peptides; Phase transitions; Polypeptides; Solid tumors; Tumor cell lines; Tumors; p50; drug delivery; cell penetrating peptide; elastin-like polypeptide
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202000170

The application of rationally designed therapeutic peptides (TP) may improve outcomes in cancer treatment. These peptides hold the potential to directly target proliferative pathways and stimulate cell arrest or death pathways. Elastin‐like polypeptide (ELP) is an elastin derived biopolymer that undergoes a thermally mediated phase transition. This study employs p50, a nuclear localization sequence derived peptide that inhibits the activation of NFκB and is implicated in cancer cell survival and metastasis. In order to effectively delivery p50, it is conjugated to SynB1‐ELP1, a thermally responsive macromolecular carrier. By applying an external heat source, mild hyperthermic conditions (41 °C) induce aggregation and therefore can be used to specifically target ELP to solid tumors in cancer therapy. The addition of a cell penetrating peptide (CPP) to the N‐terminus of the macromolecular carrier enhances the cellular uptake and directs the subcellular localization of the bioactive peptide. The novel TP, p50, inhibits proliferation and induces apoptosis of breast cancer cells by blocking the intranuclear import of NFκB. By expanding the repertoire of oncogenic targets, CPPs, and ELP carrier sizes, ELP‐based polypeptides may be modulated to optimize the delivery of these novel therapies and allow for the flexibility to create individualized cancer therapies.
The NFκB inhibitory peptide, p50, can be targeted to inhibit the growth of mammary cancers. Conjugation of p50 to SynB1‐elastin‐like polypeptide (ELP) improves peptide plasma stability and enhances the intracellular uptake. The NFκB pathway is a novel target for ELP delivered peptides and may prove to be a potent target in vivo, especially in combination with traditional therapies.