Temperature-controlled magnetic nanoparticles hyperthermia inhibits primary tumor growth and metastases dissemination

• Published in: Nanomedicine Vol. 25; p. 102171
• Main Authors: Garanina, Anastasiia S., Naumenko, Victor A., Nikitin, Aleksey A., Myrovali, Eirini, Petukhova, Anna Y., Klimyuk, Svetlana V., Nalench, Yulia A., Ilyasov, Artem R., Vodopyanov, Stepan S., Erofeev, Alexander S., Gorelkin, Peter V., Angelakeris, Makis, Savchenko, Alexander G., Wiedwald, Ulf, Majouga Dr, Alexander G., Abakumov, Maxim A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020
• Subjects: Cobalt ferrite nanoparticles; Magnetic hyperthermia; Metastasis; Murine tumor models; Temperature-dependent heating; PS; Cobalt ferrite nanoparticles; DLS; XRD; Metastasis; PDI; FBS; SLP; EDX; MHT; Magnetic hyperthermia; AMF; MNPs; Temperature-dependent heating; Hsp; s.c; i.p; i.t; AES; i.v; IVIS; ROS; Murine tumor models; SEM; TEM
• DOI: 10.1016/j.nano.2020.102171
• ISSN: 1549-9634; 1549-9642

Magnetic hyperthermia (MHT) is a promising approach for cancer therapy. However, a systematic MHT characterization as function of temperature on the therapeutic efficiency is barely analyzed. Here, we first perform comparative temperature-dependent analysis of the cobalt ferrite nanoparticles-mediated MHT effectiveness in two murine tumors models – breast (4T1) and colon (CT26) cancer in vitro and in vivo. The overall MHT killing capacity in vitro increased with the temperature and CT26 cells were more sensitive than 4T1 when heated to 43 °C. Well in line with the in vitro data, such heating cured non-metastatic CT26 tumors in vivo, while only inhibiting metastatic 4T1 tumor growth without improving the overall survival. High-temperature MHT (>47 °C) resulted in complete 4T1 primary tumor clearance, 25–40% long-term survival rates, and, importantly, more effective prevention of metastasis comparing to surgical extraction. Thus, the specific MHT temperature must be defined for each tumor individually to ensure a successful antitumor therapy. Controlled magnetic hyperthermia (MHT) provided by cobalt ferrite nanoparticles under alternating magnetic field exposure has different effects on tumor cells in vitro and in vivo depending on the temperature. The number of apoptotic and necrotic cells in cultures increases with temperature. Interestingly, delayed effect of the heating at 42–43 °C (mild MHT) varies in different cell lines. In vivo data further shows that mild MHT is not effective for metastatic 4T1 tumor therapy, while it is efficient for curing non-metastatic CT26-bearing mice. MHT at 46–48 °C and 58–60 °C increases long-term survival of 4T1-bearing mice providing primary tumor clearance and metastasis inhibition. [Display omitted]