Editors' ChoiceCancer Nanotechnology

Gold photothermal therapy: A positive for negative margins

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Science Translational Medicine  10 Jan 2018:
Vol. 10, Issue 423, eaar7512
DOI: 10.1126/scitranslmed.aar7512


Nanoparticle-based photothermal therapy after tumor resection inhibits recurrence.

Photothermal therapy (PTT) enables local therapeutic hyperthermia of tissue using a laser to convert light into heat. The concept of PTT has existed for decades, with prominent developments relying on noble-metal materials formed into varying shapes, including gold nanospheres, shells, rods, cages, and triangular bipyramids. Nanostructure shape and composition impact both localized surface plasmonic resonance behavior, which drives photothermal conversion, and passive accumulation in solid tumors via the enhanced permeability and retention (EPR) effects, which are thought to arise from tumor features including vascular hyperpermeability and local inflammation.

Preclinical studies primarily in mice have repeatedly shown that PTT safely treats superficial xenograft tumors, and PTT using gold nanoshells (AuroLase, Nanospectra) has reached pilot clinical trials for metastatic disease (NCT01679470; NCT00848042). The use of nanoparticles to achieve local hyperthermia is a validated treatment strategy in patients; alternating magnetic fields can locally heat iron oxide nanoparticles, and this approach is clinically approved in Europe to treat glioblastoma (NanoTherm, Magforce). However, physical constraints of light penetration through tissue (generally <1 cm), high-power laser intensities that are potentially damaging to healthy tissue and mixed EPR effects and nanoparticle delivery efficiencies in patients have slowed PTT clinical translation.

In a recent study, Wang and colleagues addressed some of these issues by adapting PTT to a potentially more suitable therapeutic application compared with its conventional use of treating solid tumors with a focused laser beam. The group used recently developed gold bipyramidal nanoparticles coated with polyethylene glycol. The bipyramidal nanostructure showed some preferable photothermal properties, negligible off-target toxicity was observed, and tumoral accumulation in an orthotopic breast cancer mouse model was within the range found with clinical-grade nanoparticles of similar size. Despite these features, the authors recognized that conventional PTT was still limited. Given the poor penetration of PTT to deep tissues, the authors hypothesized that more evenly distributed laser illumination could be used locally to safely treat tissue made accessible to PTT after tumor resection—tissue which may contain residual cancer cells. Histological examination suggested surgical resection alone could achieve frankly negative tumor margins, yet eventual tumor recurrence post-surgery in all animals revealed that surgery failed to completely eliminate all cancer cells. Encouragingly, post-surgical PTT decreased rates of such local tumor recurrence with minimal scarring compared with conventional PTT. This study shines light on a new strategy for using PTT as an adjuvant therapy in the clinic and complements other recent PTT developments, such as its use to stimulate antitumor immune responses when combined with anti-CTLA4 antibody treatment or similar immune checkpoint blockade therapies.

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