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Palladium Based Nanoparticles for the Treatment of Advanced Melanoma

Palladium Based Nanoparticles for the Treatment of Advanced Melanoma

Justin Elsey, Jeffrey A Bubley, Lei Zhu, Shikha Rao, Maiko Sasaki, Brian P Pollack, Lily Yang, Jack L Arbiser

Sci Rep. 2019 Mar 1;9(1):3255.

PMID: 30824801

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP202656131	Tris(hydroxymethyl-d3)amino-d2-methane		202656-13-1	Price

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