Delivering Therapeutic Heat to Solid Tumors: Bringing Practical Photothermal Therapy to the Clinic

L. Pagliaro
Siva Therapeutics, Inc.,
United States

Keywords: drug delivery, tumor, phototherapy

Summary:

Siva Therapeutics is developing a simple, safe, and effective cancer treatment termed Targeted Hyperthermia™, which generates therapeutic heat (44°C) emanating from within solid tumors using systemically injected precision gold nanorods and an infrared light engine – technology termed photothermal therapy. Heat has several beneficial effects for solid tumors, including selective induction of apoptosis in cancer cells, stimulation of the immune system, inactivation of cancer stem cells, and increased tumor perfusion resulting in improved drug efficacy. These beneficial effects of hyperthermia do not occur with ablation, which is typically 55°C and above. 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 been 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 photohermal therapy in particular, has demonstrated efficacy, both in animal models, and now in the clinic. A critical hurdle for photothermal therapy has been scaling up manufacture of nanoparticles, 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, the FDA, and NIST. 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 a second-generation LED-based infrared light engine with the ability to illuminate regions of ~10 cm in diameter with high intensity infrared light to excite nanorods that have concentrated in tumors. Together, these advances have made nanotechnology-enabled photothermal therapy safer, more practical, and more cost-effective than was previously possible.