Preclinical Studies for Nanoparticle-Enabled Photothermal Therapy: Progress and Challenges

L. Pagliaro
Siva Therapeutics Inc.,
United States

Keywords: nanorods, photothermal, cancer therapy, therapeutic heat

Summary:

Siva Therapeutics is developing a safe and effective cancer treatment termed Targeted Hyperthermia™, which generates therapeutic heat emanating from within solid tumors using systemically injected gold nanorods and an infrared light engine – technology termed photothermal therapy. Heat (~44°C) has several beneficial effects for solid tumors, including stimulation of the immune system, selective induction of apoptosis in cancer cells, inactivation of cancer stem cells, and increased perfusion resulting in improved drug efficacy. Targeted Hyperthermia provides precision heating of tumors with minimal collateral damage, using SivaRods™ polymer-coated gold nanorods and a SivaLum™ infrared light engine, and it promises to be a valuable adjunct to current drug therapies. While awareness of the therapeutic value of hyperthermia has grown in the cancer community for many decades, implementing practical, safe, and cost effective hyperthermic cancer therapy has been challenging. Nanotechnology provides key tools for targeting heat to tumors, and photothermal therapy has demonstrated efficacy, both in animal models, and now in the clinic. A critical hurdle for photothermal therapy has been scaling manufacture of nanoparticles to pilot batch size, while maintaining plasmonic properties and uniformity of the material. Siva has accomplished pilot scale manufacturing and has completed full characterization of SivaRods through the Nanotechnology Characterization Laboratory program (https://ncl.cancer.gov/), which is supported by the National Cancer Institute and the FDA. Systemically injected SivaRods have an excellent safety profile: they are neutral, inert, non-toxic, and excreted in both the urine and the feces. Additionally, Siva is developing an infrared light engine with the ability to illuminate tissues with infrared light to excite nanorods that have concentrated in tumors. Together, these advances have made nanotechnology-enabled photothermal cancer therapy safer, more practical, and more cost-effective than was previously possible. However, significant hurdles for nanotechnology-enabled treatments must be passed before entering the clinic; this presentation will review the many challenges facing this therapeutic approach.