PEGylated rhenium nanoclusters: a degradable metal photothermal nanoagent for cancer therapy

Abstract

A common issue of functional nanoagents for potential clinical translation is whether they are biodegradable or renal clearable. Previous studies have widely explored noble metal nanoparticles (Au and Pd) as the first generation of photothermal nanoagents for cancer therapy, but all of the reported noble metal nanoparticles are non-degradable. On the other hand, rhenium (Re), one of the noble and precious metals with a high atomic number (Z = 75), has been mainly utilized as a jet superalloy or chemical catalyst, but the biological characteristics and activity of Re nanoparticles have never been evaluated until now. To address these issues, here we report a simple and scalable liquid-reduction strategy to synthesize PEGylated Re nanoclusters, which exhibit intrinsically high photothermal conversion efficacy (33.0%) and high X-ray attenuation (21.2 HU mL mg⁻¹), resulting in excellent photothermal ablation (100% tumor elimination) and higher CT enhancement (15.9 HU mL mg⁻¹ for commercial iopromide in clinics). Impressively, biocompatible Re nanoclusters can degrade into renal clearable ReO₄⁻ ions after exposure to H₂O₂, and thus achieve much higher renal clearance efficiency than conventional gold nanoparticles. This work reveals the potential of theranostic application of metallic Re nanoclusters with both biodegradation and renal clearance properties and provides insights into the design of degradable metallic platforms with high clinical prospects.