TY - JOUR
T1 - Synergized photothermal therapy and magnetic field induced hyperthermia via bismuthene for lung cancer combinatorial treatment
AU - Yilmazer, Açelya
AU - Eroglu, Zafer
AU - Gurcan, Cansu
AU - Gazzi, Arianna
AU - Ekim, Okan
AU - Sundu, Buse
AU - Gokce, Cemile
AU - Ceylan, Ahmet
AU - Giro, Linda
AU - Unal, Mehmet Altay
AU - Arı, Fikret
AU - Ekicibil, Ahmet
AU - Ozgenç Çinar, Ozge
AU - Ozturk, Berfin Ilayda
AU - Besbinar, Omur
AU - Ensoy, Mine
AU - Cansaran-Duman, Demet
AU - Delogu, Lucia Gemma
AU - Metin, Onder
N1 - Funding Information:
A.Y. and Ö.M. thank to the Turkish Academy of Sciences (TUBA) for the financial support. C.G. and O.B. would like to thank to the Council of Higher Education (YOK) for the YOK100/2000 PhD scholarships. L.G.D wishes to thank UNIPD for the start up grant 2020. A.Y. and L.G.D. would like to thank the European Commission HORIZON Marie Sklodowska-Curie Actions ( MSCA ) Staff Exchanges 2021 grant. Authors would like to thank Merve Evren for the study illustration in Fig. 1 .
Funding Information:
Bismuthene-treated A549 cells were simultaneously exposed to 850 nm light and a magnetic field (50 Hz, 600 mA). As shown in Fig. 4A, simultaneous light and magnetic field exposure resulted in 100% cell death in A549 cells. These findings were further supported by apoptosis assays in which cells were stained with Annexin-FITC/PI after various treatments. Both necrosis and apoptosis were found to play roles in cell death after simultaneous light and magnetic field exposure to bismuthene-treated cells (Fig. 4B). To demonstrate that magnetic field exposure resulted in hyperthermia, we analyzed temperature changes in culture media. As shown in Fig. 4C, the highest temperature change was obtained when the cells were exposed to both light irradiation and a magnetic field, and the effect was concentration-dependent. PDT- and PTT-dependent tumor cell death is well known to result in ICD, activating immune cells. The surface expression of calreticulin is an important indicator of ICD [9]. Therefore, to show that simultaneous light and magnetic field exposure of bismuthene induced ICD, we stained treated cells with anti-calreticulin antibody and analyzed them through flow cytometry. As shown in Fig. 4D, the expression of calreticulin was significantly higher in the dual exposed and bismuthene treated A549 cells, thus indicating that bismuthene-based PTT and MH induced ICD. In addition to calreticulin expression, levels of ATP or HMGB1 in cell culture media are other markers of ICD. As can be seen in Fig. 4E and F, both HMGB1 release and extracellular ATP levels were significantly higher in bismuthene treated cells following both 850 nm light irradiation and magnetic field application.A.Y. and Ö.M. thank to the Turkish Academy of Sciences (TUBA) for the financial support. C.G. and O.B. would like to thank to the Council of Higher Education (YOK) for the YOK100/2000 PhD scholarships. L.G.D wishes to thank UNIPD for the start up grant 2020. A.Y. and L.G.D. would like to thank the European Commission HORIZON Marie Sklodowska-Curie Actions (MSCA) Staff Exchanges 2021 grant. Authors would like to thank Merve Evren for the study illustration in Fig. 1.
Publisher Copyright:
© 2023
PY - 2023/12
Y1 - 2023/12
N2 - Thanks to its intrinsic properties, two-dimensional (2D) bismuth (bismuthene) can serve as a multimodal nanotherapeutic agent for lung cancer acting through multiple mechanisms, including photothermal therapy (PTT), magnetic field-induced hyperthermia (MH), immunogenic cell death (ICD), and ferroptosis. To investigate this possibility, we synthesized bismuthene from the exfoliation of 3D layered bismuth, prepared through a facile method that we developed involving surfactant-assisted chemical reduction, with a specific focus on improving its magnetic properties. The bismuthene nanosheets showed high in vitro and in vivo anti-cancer activity after simultaneous light and magnetic field exposure in lung adenocarcinoma cells. Only when light and magnetic field are applied together, we can achieve the highest anti-cancer activity compared to the single treatment groups. We have further shown that ICD-dependent mechanisms were involved during this combinatorial treatment strategy. Beyond ICD, bismuthene-based PTT and MH also resulted in an increase in ferroptosis mechanisms both in vitro and in vivo, in addition to apoptotic pathways. Finally, hemolysis in human whole blood and a wide variety of assays in human peripheral blood mononuclear cells indicated that the bismuthene nanosheets were biocompatible and did not alter immune function. These results showed that bismuthene has the potential to serve as a biocompatible platform that can arm multiple therapeutic approaches against lung cancer.
AB - Thanks to its intrinsic properties, two-dimensional (2D) bismuth (bismuthene) can serve as a multimodal nanotherapeutic agent for lung cancer acting through multiple mechanisms, including photothermal therapy (PTT), magnetic field-induced hyperthermia (MH), immunogenic cell death (ICD), and ferroptosis. To investigate this possibility, we synthesized bismuthene from the exfoliation of 3D layered bismuth, prepared through a facile method that we developed involving surfactant-assisted chemical reduction, with a specific focus on improving its magnetic properties. The bismuthene nanosheets showed high in vitro and in vivo anti-cancer activity after simultaneous light and magnetic field exposure in lung adenocarcinoma cells. Only when light and magnetic field are applied together, we can achieve the highest anti-cancer activity compared to the single treatment groups. We have further shown that ICD-dependent mechanisms were involved during this combinatorial treatment strategy. Beyond ICD, bismuthene-based PTT and MH also resulted in an increase in ferroptosis mechanisms both in vitro and in vivo, in addition to apoptotic pathways. Finally, hemolysis in human whole blood and a wide variety of assays in human peripheral blood mononuclear cells indicated that the bismuthene nanosheets were biocompatible and did not alter immune function. These results showed that bismuthene has the potential to serve as a biocompatible platform that can arm multiple therapeutic approaches against lung cancer.
KW - Bismuthene
KW - Cancer therapy
KW - Magnetic field induced hyperthermia
KW - Photothermal therapy
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U2 - 10.1016/j.mtbio.2023.100825
DO - 10.1016/j.mtbio.2023.100825
M3 - Article
AN - SCOPUS:85173159380
SN - 2590-0064
VL - 23
JO - Materials Today Bio
JF - Materials Today Bio
M1 - 100825
ER -