Over the last few decades, gold nanoparticles (GNPs) have emerged as "radiosensitizers" in oncology. Radiosensitizers are additives that can enhance the effects of radiation on biological tissues treated with radiotherapy. The interaction of photons with GNPs leads to the emission of low-energy and short-range secondary electrons, which in turn increase the dose deposited in tissues. In this context, GNPs are the subject of intensive theoretical and experimental studies aiming at optimizing the parameters leading to greater dose enhancement and highest therapeutic effect. This review describes the main mechanisms occurring between photons and GNPs that lead to dose enhancement. The outcome of theoretical simulations of the interactions between GNPs and photons is presented. Finally, the findings of the most recent in vivo studies about interactions between GNPs and photon sources (e.g., external beams, brachytherapy sources, and molecules labeled with radioisotopes) are described. The advantages and challenges inherent to each of these approaches are discussed. Future directions, providing new guidelines for the successful translation of GNPs into clinical applications, are also highlighted.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with diameters <5 nm hold great promise as T1-positive contrast agents for in vivo magnetic resonance imaging. However, control of the surface chemistry of USPIOs to ensure individual colloidal USPIOs with a ligand monolayer and to impart biocompatibility and enhanced colloidal stability is essential for successful clinical applications. Herein, an effective and versatile strategy enabling the development of aqueous colloidal USPIOs stabilized with well-defined multidentate block copolymers (MDBCs) is reported. The multifunctional MDBCs are designed to consist of an anchoring block possessing pendant carboxylates as multidentate anchoring groups strongly bound to USPIO surfaces and a hydrophilic block having pendant hydrophilic oligo(ethylene oxide) chains to confer water dispersibility and biocompatibility. The surface of USPIOs is saturated with multiple anchoring groups of MDBCs, thus exhibiting excellent long-term colloidal stability as well as enhanced colloidal stability at biologically relevant electrolyte, pH, and temperature conditions. Furthermore, relaxometric properties as well as in vitro and in vivo MR imaging results demonstrate that the MDBC-stabilized USPIO colloids hold great potential as an effective T1 contrast agent.

Prostate cancer (PCa) is one of the leading causes of death among men. Low-dose brachytherapy is an increasingly used treatment for PCa, which requires the implantation of tens of radioactive seeds. This treatment causes discomfort; these implants cannot be removed, and they generate image artifacts. In this study, the authors report on intratumoral injections of radioactive gold nanoparticles (Au NPs) as an alternative to seeds. The particles ( Pd:Pd@Au-PEG and Pd:Pd@ Au:Au-PEG; 10-14 nm Pd@Au core, 36-48 nm hydrodynamic diameter) are synthesized by a one-pot process and characterized by electron microscopy. Administrated as low volume (2-4 µL) single doses (1.6-1.7 mCi), the particles are strongly retained in PCa xenograft tumors, impacting on their growth rate. After 4 weeks, a tumor volume inhibition of 56% and of 75%, compared to the controls, is observed for Pd:Pd@Au-PEG NPs and Pd:Pd@ Au:Au-PEG NPs, respectively. Skin necrosis is observed with Au; therefore, Au NPs labeled with Pd only are a more advisable choice. Overall, this is the first study confirming the impact of Pd@Au NPs on tumor growth. This new brachytherapy procedure could allow tunable doses of radioactivity, administered with smaller needles than with the current technologies, and leading to fewer image artifacts.