Palladium based nanoparticles for the treatment of advanced melanoma

• Type of Material: Article
• Authors: Justin Elsey, Emory University; Jeffrey A. Bubley, Emory University; Lei Zhu, Emory University; Shikha Rao, Emory University; Maiko Sasaki, Emory University; Brian Pollack, Emory University; Lily Yang, Emory University; Jack Arbiser, Emory University
• Language: English
• Date: 2019-03-01
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-019-40258-6
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 9
• Issue: 1
• Start Page: 3255
• End Page: 3255
• Keywords: MELANOCYTES; INDUCTION; Science & Technology; TRIS DIBENZYLIDENEACETONE DIPALLADIUM; Multidisciplinary Sciences; FIBROBLAST-GROWTH-FACTOR; TARGETS; EXPRESSION; ACTIVATION; INHIBITOR RESISTANCE; DBA PALLADIUM; PANCREATIC-CANCER; Science & Technology - Other Topics
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

IGF1R and CD44 are overexpressed in most advanced melanomas so we designed chemotherapeutic nanoparticles to target those receptors. Tris(dibenzylideneacetone)dipalladium (Tris DBA-Pd) is a novel inhibitor of N-myristoyltransferase 1 (NMT-1) and has proven in vivo activity against melanoma. However, poor solubility impairs its effectiveness. To improve its therapeutic efficacy and overcome drug resistance in advanced melanomas, we synthesized Tris DBA-Pd hyaluronic acid nanoparticles (Tris DBA-Pd HANP) and evaluated them against in vivo xenografts of LM36R, an aggressive BRAF mutant human melanoma resistant to BRAF inhibitors. We treated xenografted mice in four arms: empty HANPs, free Tris DBA-Pd, Tris DBA-Pd HANPs, and Tris DBA-Pd HANPs with IGF1R antibody. The Tris DBA-Pd HANP group was the most responsive to treatment and showed the greatest depletion of CD44-positive cells on IHC. Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.