A Spiky Silver‐Iron Oxide Nanoparticle for Highly Efficient Targeted Photothermal Therapy and Multimodal Imaging of Thrombosis

Abstract

Thrombosis and its complications are responsible for 30% of annual deaths. Limitations of methods for diagnosing and treating thrombosis highlight the need for improvements. Agents that provide simultaneous diagnostic and therapeutic activities (theranostics) are paramount for an accurate diagnosis and rapid treatment. In this study, silver‐iron oxide nanoparticles (AgIONPs) are developed for highly efficient targeted photothermal therapy and imaging of thrombosis. Small iron oxide nanoparticles are employed as seeding agents for the generation of a new class of spiky silver nanoparticles with strong absorbance in the near‐infrared range. The AgIONPs are biofunctionalized with binding ligands for targeting thrombi. Photoacoustic and fluorescence imaging demonstrate the highly specific binding of AgIONPs to the thrombus when functionalized with a single chain antibody targeting activated platelets. Photothermal thrombolysis in vivo shows an increase in the temperature of thrombi and a full restoration of blood flow for targeted group but not in the non‐targeted group. Thrombolysis from targeted groups is significantly improved (p < 0.0001) in comparison to the standard thrombolytic used in the clinic. Assays show no apparent side effects of AgIONPs. Altogether, this work suggests that AgIONPs are potential theranostic agents for thrombosis.

Spiky Silver–Iron Oxide Nanohybrid for Effective Dual-Imaging and Synergistic Thermo-Chemotherapy

“…The iron oxide core also functioned as a surface template for the silver ion coating and acted as a donor of electrons for the growth of the Ag layer. The silver coating was formed via a seeding technique, whereby reducing agents were employed to reduce the salts in the silver nitrate solution . Here, the seedings of silver nucleation were developed by the utilization of sodium citrate, hydroxylamine, and the citrate-coated iron oxide nanoparticles.…”

“…Subsequently, the addition of silver nitrate aliquots formed a silver seed on the surface of the IONPs. Previously reported studies from our group have demonstrated that the mass ratio between silver and iron (Ag/Fe) and the amount of hydroxylamine employed are crucial for the asymmetrical spiky shaped NPs and their strong absorbance in the NIR. , The optimized protocol involves the utilization of 20 μL of 50% hydroxylamine and a 1.18 mass ratio of Ag/Fe in the reaction. It should be noted that preliminary imaging studies of NPs were performed to ascertain both MRI and PAI contrast abilities to confirm parameters such as the Ag/Fe ratios in the synthesis reaction as these NPs were developed to be effective in both photothermal treatment strategy and dual-imaging ability using MRI and PAI.…”

“…An additional 75 μL of TSC (1.14%) was added at the end of the synthesis to stabilize the nanoparticles. The dense silver-coated iron oxide particles were separated from the less dense uncoated particles by centrifugation at 3500 g for 7 min and redispersed in deionized (DI) water . Dialysis was performed overnight with 5 L of water to purify the nanoparticles.…”

“…The silver coating was formed via a seeding technique, whereby reducing agents were employed to reduce the salts in the silver nitrate solution. 39 Here, the seedings of silver nucleation were developed by the utilization of sodium citrate, hydroxylamine, and the citrate-coated iron oxide nanoparticles. Subsequently, the addition of silver nitrate aliquots formed a silver seed on the surface of the IONPs.…”

Multiwalled Carbon Nanotubes Decorated with Mn0.5Zn0.5Fe2O4 Nanoparticles for Magneto-Photothermal Cancer Therapy

“…Two types of hyperthermia depending on the stimulus used as a trigger, i.e ., optical or magnetic properties activated nanoheating agents. Magnetic hyperthermia (MHT) utilizes heat dissipation by MNPs to kill tumor cells when under an alternating magnetic field (AMF), − while photothermal therapy (PTT) employs photothermal agents that are activated by near-infrared laser (NIR) irradiation. − However, both magnetic hyperthermia and photothermal therapy have their limitations. , For instance, highly concentrated intratumoral injections of magnetic nanoparticles are required to compensate the low specific loss power (SLP) under low magnetic field intensity for the MHT, the real-time temperature monitoring is invasive thermometry, and the nanoparticles distribute non-uniformly within the tumor . Therefore, enhancing SLP value through modifications in the material properties, size, shape, and aggregation state of magnetic nanoparticles emerges as the pivotal factor for augmenting the effectiveness of magnetic hyperthermia. − In PTT, high-power laser exposure can damage surrounding healthy tissue, and some nanoparticles (gold and silver) used are not FDA-approved materials and may not meet biosafety requirements .…”