Sensitization of Cancer Cells via Non‐Viral Delivery of Apoptosis Inducing Proteins Using a Cationic Bolaamphiphile

• Published in: Biotechnology journal 2019-03, Vol.14 (3), p.e1800020-n/a
• Main Authors: Narayanan, Karthikeyan, Khan, Majad, Gopalan, Began, Antony, Jane, Das, Tultul, Yang, Yi Yan, Wan, Andrew C. A.
• Format: Article
• Language: English
• Subjects: cationic bolaamphiphile; p53; protein delivery; sensitization of cancer cells; survivin antibody
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.201800020

Cationic bolaamphiphile polymers had been previously studied as efficient delivery system for the delivery of proteins with relatively low toxicity. Here, the authors investigate the use of a protein delivery system based on a cationic bolaamphiphile to sensitize cancer cells toward apoptosis‐inducing drugs as a novel approach for cancer therapy. The authors demonstrates the efficacy of the system by two strategies. The first strategy involves delivery of a survivin antibody to inhibit survivin activity. Sensitization of MCF‐7 cells to doxorubicin is observed by survivin inhibition by antibodies. The IC50 of doxorubicin is reduced ≈2.5‐fold after delivery of survivin antibodies to breast cancer cells and induction of apoptosis is shown by Western blotting with apoptosis specific antibodies. In a second approach, functional wild type p53 is delivered into p53‐null liver cancer (Hep3B) cells, sensitizing the cells toward the p53 pathway drug, Nutlin. Nutlin reduced the viability of Hep3B cells by ≈42% at 15 μM concentration, demonstrating the effectiveness of p53 delivery. The expression of p21, a downstream target of p53 further confirmed the functional status of the delivered protein. In conclusion. The successful delivery of apoptosis inducing proteins and sensitization of cancer cells via cationic bolaamphiphile polymer represents a promising system for cancer therapeutics. Bolaamphiphiles containing hydrophilic and hydrophobic domains are complexed with cell death promoting proteins (inducers of apoptosis) to form micelles. Chemotherapeutic drug sensitivity of cancer cells is increased upon internalization of these micelles.