Lily Yang, Jack Arbiser, and Colleagues Test New Nanoparticle as Therapy for Advanced Melanoma

March 2019

An Emory team of researchers from the departments of dermatology and surgery that included co-investigator Lily Yang, MD, PhD, Nancy Panoz Chair of Surgery in Cancer Research, and principal investigator Jack Arbiser, MD, PhD, Thomas J. Lawley Professor of Dermatology, published the results of a study investigating the delivery of a novel agent for melanoma using nanoparticles on March 1 in Scientific Reports.

Dr. Arbiser, Dr. Yang, and colleagues set out to design chemotherapeutic nanoparticles that would target the IGF1R and CD44 protein receptors that are crucial for tumor growth and excessively expressed in most advanced melanomas. They focused on synthesizing a new nanoparticle (NP) that incorporated the organometallic compound Tris(dibenzylideneacetone)dipalladium (Tris DBA-Pd), which Dr. Arbiser's laboratory had already shown to be an effective combatant of melanoma in preclinical models, with hyaluronic acid (HA), a reliable vehicle in the targeted delivery of anticancer drugs. The group hoped that creating this NP would solve the problem of Tris DBA-Pd's poor solubility, which restricted its effectiveness.

The team evaluated the new particles, known as Tris DBA-Pd HANPs, against in vivo xenografts in mice of LM36R, a particularly aggressive form of melanoma that is resistant to the BRAF inhibitors used to treat those melanomas whose growth is aided by mutant BRAF genes — normal BRAF genes send signals inside cells that assist in directing non-harmful cell growth. The mice were separated into four treatment arms, with one group receiving just HANPs, another injections of just Tris DBA-Pd, the third Tris DBA-Pd HANPs, and the fourth Tris DBA-Pd HANPs with IGF1R antibody.

The study found that the Tris DBA-Pd HANP group was the most responsive to treatment and showed the greatest depletion of CD44-positive cells, leading Dr. Yang, Dr. Arbiser, and their co-researchers to conclude that the new NPs were an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.