Self-Dissolving Tetrathiomolybdate Implant for Long-Term Copper Starvation of Solid Tumours

This work presents a passive, localized therapeutic strategy for the metabolic collapse of solid tumors through continuous copper depletion. The proposed approach uses a slow-release biodegradable implant composed of poly-ε-caprolactone (PCL) and microdoses of tetrathiomolybdate (TM), a copper-selective chelator with an 8-log selectivity for Cu²⁺ over Zn²⁺. Although TM demonstrated exceptional biochemical potential, its prior systemic applications (oral and intravenous) failed due to non-specific depletion of hepatic and hematopoietic copper reserves before reaching the tumor site. The drug was discarded not because it was ineffective, but because it was misdelivered. This study reintroduces TM in its correct context: not systemically, but embedded directly inside the tumor mass, where it maintains a local diffusion front capable of sequestering mitochondrial copper. This results in a controlled loss of oxidative phosphorylation capacity, inhibition of angiogenesis, and progressive apoptotic failure in the tumor, without systemic toxicity. The implant requires no electronics, no targeting ligand, no activation; it operates by material logic, using tumor physiology as the mechanism of execution. The TM capsule is low-cost, biocompatible, and based entirely on materials already validated in human use. It is proposed as a scalable alternative to high-toxicity chemotherapy for tumors with elevated copper dependence. This manuscript aims to rescue a clinically promising molecule that was unjustly abandoned due to delivery errors, and to establish a precise, accessible method of tumor control through metabolic starvation.