Neutron-Activatable Holmium-Containing Nanoparticles for the Treatment of Non-small Cell Lung and Skin Cancers




Shi, Yi
Munaweera, Imalka
Koneru, Bhuvaneswari
Levesque-Bishop, Daniel
Aliev, Ali
Coyle, Russell
Saez, Ruben
Balkus, Kenneth J.
Di Pasqua, Anthony J.


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Purpose: To improve therapeutic outcomes for patients with non-small cell lung and skin cancers using radiation therapy. Methods: Magnetic holmium-165 (Ho) nanoparticles (HoIG) and derivatives containing platinum-based chemotherapeutic drugs (HoIG-Pt) were prepared and then neutron-activated to radioactive holmium-166 (166Ho; Eβ-max = 1.84 MeV; t½ = 26.8 h) nanoparticles (166HoIG and 166HoIG-Pt, respectively). Cytotoxicities of 166HoIG and 166HoIG-Pt were tested against non-small cell lung cancer cells, and in vivo studies were performed. 165HoIG were also introduced into poly-acrylonitrile (PAN) polymer solutions; these solutions were electrospun to produce bandages that can be applied directly to tumor lesions after neutron-activation. Results: Ho materials were carefully characterized and successfully neutron-activated. HoIG contained approximately 56% w/w Ho. Two 166HoIG-Pt derivatives showed greater toxicity toward non-small cell lung cancer cells than blank 166HoIG and free platinum drug. The animal study data collected showed that the radiation and platinum drug act synergistically. HoIG was distributed homogenously throughout the radioactive bandages and the bandage was stable upon neutron-activation. Conclusion: Pt-based chemotherapeutic drugs and 166Ho have been incorporated together in a magnetic nanoparticle for the first time, and then used successfully in human cell culture and animal studies. A novel radiotherapeutic bandage was successfully prepared using PAN solutions and HoIG nanoparticles, and subsequently neutron-activated. The radiotherapeutic bandage is a more flexible strategy than that currently being used in the clinic for the treatment of skin cancer.