Abstract
Herein, we report a novel therapy for prostate cancer based on systemically delivered magnetic hyperthermia. Conventional magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites via intratumoral administration produce heat in the presence of an alternating magnetic field (AMF). To employ this therapy for prostate cancer tumors that are challenging to inject intratumorally, we designed novel nanoclusters with enhanced heating efficiency that reach prostate cancer tumors after systemic administration and generate desirable intratumoral temperatures upon exposure to an AMF. Our nanoclusters are based on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome the challenges associated with the poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL (methoxy poly(ethylene glycol)-b-poly(ε-caprolactone))-based polymeric nanoparticles. Animal studies demonstrated that, following intravenous injection into mice bearing prostate cancer grafts, the nanoclusters efficiently accumulated in cancer tumors within several hours and increased the intratumoral temperature above 42 °C upon exposure to an AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibited prostate cancer growth and did not exhibit any signs of toxicity.
Highlights
The high mortality rate among prostate cancer patients is attributed to the fact that there is no effective cure once the disease has spread beyond the prostate
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We have successfully developed novel nanoclusters of zinc- and manganese-doped iron oxide nanoparticles encapsulated inside PEG-PCL-based polymeric vehicles
Summary
The high mortality rate among prostate cancer patients is attributed to the fact that there is no effective cure once the disease has spread beyond the prostate. Magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles produce high temperatures at cancer sites in the presence of a noninvasive alternating magnetic field (AMF). This feature allows a remote elevation of the intratumoral temperature while minimizing the heating of healthy tissue [3,4]. Conventional magnetic hyperthermia, is restricted to the treatment of accessible tumors because therapeutically relevant temperatures (>40 ◦C) are only reached following the intratumoral administration of magnetic nanoparticles [16,17] This is due to the relatively low tumor accumulation and heating efficiency of conventional iron oxide nanoparticles following systemic delivery. Systemically delivered magnetic hyperthermia has not yet been explored for the treatment of various types of cancer, including prostate cancer
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