Delivery of Retinoic Acid Utilizing Cell Penetrating Peptides in Human Neuroblastoma Cells

Abstract

Cancer is the second leading cause of death in America. In 2018, there were 9.5 million deaths due to cancer according to the International Agency for Research on Cancer (IARC), and this number is expected to grow to 16.3 million by 2040. Among the type of cancers, neuroblastoma and nerve tissue cancers have a 5-year survival rate of 33%, which is very low. One of the main issues linked to such situations is due to the lack of specificity in removing tumor cells. While clinical therapies work to reduce tumor mass as much as possible, they cannot always target all of them, and once some cancer cells are left behind, they regrow and spread. The work of this thesis seeks to enhance the treatment outcome by utilizing all-trans retinoic acid (ATRA), a metabolite of vitamin A, to induce differentiation of nerve tissue cancer cells and eliminate their ability to self-renew (reemerge). Differentiation therapy is currently utilized in select clinical applications but the utilization of ATRA is limited due to its poor solubility in the blood, low bioavailability, short half-life, and in vivo toxicity. In order to alleviate some of these issues, the ATRA molecule was engineered with a novel cell penetrating peptide and tested for its efficacy. Data and results presented herein report the differentiation induced by the CPP-conjugated ATRA may act as a viable method for neuroblastoma treatment.