Hyperthermia has failed to reach its potential as an effective anti-cancer therapy due mainly to the problems associated with lack of penetrance by external heating sources, heat damage to normal tissues and the invasiveness of some approaches (e.g. interstitial hyperthermia). Even the more promising use of magnetic nanoparticles is currently limited due to lack of available effective tumor-targeting systemic delivery. None of the current approaches can efficiently treat disseminated (metastatic) cancer. Our anti-transferrin receptor scFv immunoliposome (scL) is a systemically administered, tumor-targeting nanocomplex (approximately 100nm) for delivery of molecular medicines. It efficiently and specifically delivers various payloads to tumor cells in vivo, and is in Phase I clinical trials for p53 gene therapy. We modified the scL complex to encapsulate superparamagnetic iron oxide (SPIO). We demonstrated that the scL nanocomplex can transport SPIO specifically and efficiently into primary and metastatic tumor cells. Thus, scL-SPIO would be capable of delivering sufficient SPIO to generate therapeutic temperatures only in the tumor when the patient is exposed to an alternating magnetic field. As SPIO is also used in MRI, scL-SPIO use would allow simultaneous imaging and hyperthermic treatment. In this Phase I proposal we will optimize scL-SPIO and test its hyperthermic potential. None of the current approaches for heat therapy of cancer can efficiently treat metastases. Tumor-specific delivery of magnetic particles specifically and efficiently to tumor cells would overcome this problem and limit the exposure of normal tissue, reducing toxicity. The tumor specific, multifunctional scL-SPIO complex would allow simultaneous imaging and heat treatment of tumors, thus having a significant clinical impact.
