Modulation of in Vivo Tumor Radiation Response via Gold Nanoshell-Mediated Vascular-Focused Hyperthermia: Characterizing an Integrated Antihypoxic and Localized Vascular Disrupting Targeting Strategy

Abstract

We report noninvasive modulation of in vivo tumor radiation response using gold nanoshells. Mild-temperature hyperthermia generated by near-infrared illumination of gold nanoshell-laden tumors, noninvasively quantified by magnetic resonance temperature imaging, causes an early increase in tumor perfusion that reduces the hypoxic fraction of tumors. A subsequent radiation dose induces vascular disruption with extensive tumor necrosis. Gold nanoshells sequestered in the perivascular space mediate these two tumor vasculature-focused effects to improve radiation response of tumors. This novel integrated antihypoxic and localized vascular disrupting therapy can potentially be combined with other conventional antitumor therapies.

Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy

“…To further enhance tumor selectivity, active targeting s trategies have been pursued by many investigators. 5,6 Given the r elatively large size of NSs, 7 they are unlikely to penetrate deep into tumor parenchyma but are readily sequestered within the perivascular space. Therefore, active targeting to antigens specific to tumor cells is not expected to achieve substantially higher tumor penetration.…”

Cooperative nanomaterial system to sensitize, target, and treat tumors

“…In addition to their role as effective carriers of conventional therapeutic drugs, nanoscale materials can be harnessed to damage or destroy malignant tissues by converting external electromagnetic energy into heat (1)(2)(3)(4)(5)(6). Furthermore, most nanomaterial surfaces can be decorated with targeting ligands, enhancing their ability to home to diseased tissues through multivalent interactions with tissue-specific receptors (7).…”

Tumor-specific hyperthermia with aptamer-tagged superparamagnetic nanoparticles

“…Targeted NPs bound to receptors on the surface of cancer cells offer high effective local concentrations. 27,28 To summarize, targeted NPs combined with hyperthermia efficiently cause cell death in vitro. Application of such NPs in therapy may decrease the side effects caused by the indiscriminate killing of nontumor cells, as well as any damage to the liver, spleen, or bone marrow.…”