Journal
PHARMACEUTICS
Volume 12, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics12111020
Keywords
nanoparticle; nanocluster; magnetic hyperthermia; alternating magnetic field; prostate cancer
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Funding
- National Cancer Institute of the National Institutes of Health [R01CA237569, R37CA234006]
- National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [1R15EB020351-01A1]
- College of Pharmacy at Oregon State University
- Najran University
- Jazan University
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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(epsilon-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 degrees 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.
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