Intracellular Delivery of a p21-Derived Cell Cycle Inhibitory Peptide Using Elastin-like Polypeptides Suppresses Glioblastoma Cell Proliferation.

Glioblastoma, with a 5-year survival rate of just under 7.0%, is the most common form of brain cancer in adults. In this study, we evaluated the antiproliferative activity of the biopolymer p21-ELP1-Bac, a p21-derived peptide delivered via an elastin-like polypeptide (ELP1) carrier and a cell-penetrating peptide (CPP), across three glioblastoma cell lines: U87, GBM43, and GBM6. We assessed proliferation, cell cycle progression, and apoptosis to determine whether ELP-mediated intracellular delivery of p21-ELP1-Bac suppresses glioblastoma growth through cytostatic mechanisms rather than inducing apoptosis. Treatment with the modified protein effectively inhibited proliferation across all three lines, with U87 cells showing the greatest sensitivity and GBM6 cells demonstrating the greatest drug tolerance. Although apoptotic responses were generally low, they appeared more pronounced in GBM6 cells. Confocal microscopy revealed sustained cellular uptake and signal observed in both the cytoplasm and in proximity to the nucleus in all cell lines. Collectively, these findings indicate that p21-ELP1-Bac is efficiently internalized and capable of modulating proliferation across all three glioblastoma cell lines, supporting its further evaluation as a cytostatic delivery platform.