Temperature responsive porous silicon nanoparticles for cancer therapy - spatiotemporal triggering through infrared and radiofrequency electromagnetic heating.
One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals.



The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo.
University of Eastern Finland, Department of Applied Physics, 70211, Kuopio, Finland; M.V. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia.
Konstantin
K
Tamarov
University of Eastern Finland, Department of Applied Physics, 70211, Kuopio, Finland. Electronic address: wujun.xu@uef.fi.
Wujun
W
Xu
M.V. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia; National Research Nuclear University "MEPhI", 115409 Moscow, Russia.
Liubov
L
Osminkina
National Research Nuclear University "MEPhI", 115409 Moscow, Russia; Russian Cancer Research Blokhin Center, 115478, Moscow, Russia.
Sergey
S
Zinovyev
University of Eastern Finland, School of Pharmacy, 70211, Kuopio, Finland.
Pasi
P
Soininen
Institute of Theoretical and Experimental Biophysics of RAS, 142290, Pushino, Russia.
Andrey
A
Kudryavtsev
M.V. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia.
Maxim
M
Gongalsky
Russian Scientific Center of Medical Rehabilitation and Balneology, 121099, Moscow, Russia.
Azha
A
Gaydarova
University of Eastern Finland, School of Pharmacy, 70211, Kuopio, Finland.
Ale
A
Närvänen
M.V. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia; National Research Nuclear University "MEPhI", 115409 Moscow, Russia.
Victor
V
Timoshenko
University of Eastern Finland, Department of Applied Physics, 70211, Kuopio, Finland. Electronic address: vesa-pekka.lehto@uef.fi.
Vesa-Pekka
VP
Lehto
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D007259:Infrared Rays / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008808:Mice, Inbred CBA; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D016062:Porosity; D061208:Pulsed Radiofrequency Treatment / Q000379:methods*; D012825:Silicon / Q000737:chemistry*; D013499:Surface Properties
D000180:Acrylic Resins; D000970:Antineoplastic Agents; D004337:Drug Carriers; C052970:poly-N-isopropylacrylamide; D012825:Silicon
infrared heating; porous silicon; radiofrequency heating; temperature responsive polymer; triggered drug release