(143d) Nanoparticle/Heat-Responsive-Polymer Complex for Hyperthermia and Sustained Drug Release

Iron oxide nanoparticles (IONPs) can get heated under alternating electromagnetic (AEM) field.  They are non-toxic and have been used as a heat-delivering medium for cancer hyperthermia. Pluronic F-127 (PF127) is a biocompatible polymer that possesses both temperature and concentration-dependent gelation properties in aqueous solutions.  We have combined these two unique materials (IONPs and PF127) to develop both tumor-specific hyperthermia and long-term, sustained drug delivery. IONPs are mixed with the PF127 solution of a particular concentration, whose phase is liquid at room temperature and is semi-solid (gel) at or above the human body temperature.  The mixture of IONPs and cancer-drug containing PF127 solution is to be injected to the site of the cancer in human body.  Then the mixture becomes a gel at body temperature. AEM field is then applied to the cancer site to perform low temperature (42-45^oC) hyperthermia. For the tumor cells surviving hyperthermia, the PF127 releasing cancer-drug will treat them in a longer term.

 Our study results showed that 30 nm IONPs appeared to be highly effective for hyperthermic treatment.  The gelation temperatures of PF127 at various concentrations were determined to select the PF127 concentration that is liquid at room temperature (during injection) but becomes a gel phase at body temperature. 18% PF127 (w/w) was ideal for our purpose because it was liquid at room temperature and its gelation temperature was ~28°C.  It should be injectable at room temperature and should form a gel upon injection into human body (37°C).  Then the effect of the IONPs in the PF127 phase transition temperature was also studied.  Study results on the IONP-mixed 18% PF127 showed that the IONPs in the PF127 solution had little effect on gelation temperatures at the IONP concentration range of 0.01-0.03%.  The effect of PF127 on the IONP heating was also studied and with the addition of PF127, IONPs showed a slight decrease in heating.

 This design would be minimally-invasive and can be only to the cancer area.  It provides both hyperthermia and zero-order, sustainable drug release at the cancer site, enabling the cancer treatment in dual cancer treatment modalities and also minimizing the negative side effects of traditional, systemic cancer treatments.

 Acknowledgements: We acknowledge the BASF Global for generously supplying PF127.