One‐Minute Preparation of Iron Foam‐Drug Implant for Ultralow‐Power Magnetic Hyperthermia‐Based Combination Therapy of Tumors in Vivo

Abstract The magnetic hyperthermia‐based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)‐drug implant is established in an ultra‐facile and universal way for ultralow‐power MHCT of tumors in vivo for the first time. The IF‐drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra‐high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via “capillary action”. In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large‐scale preparation of IF‐drug implants for biological application. As a proof of concept, IF‐doxorubicin (IF‐DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF‐drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow‐power combination therapy.


Figure S2 .
Figure S2.(a) Photos of experiment on IF conductivity (turn off).(b) Photos of experiment on IF conductivity (turn on).

Figure S4 .
Figure S4.Absorbance of drug solution before and after IF loading.

Figure S5 .
Figure S5.Photos of IF and IF-DOX.

Figure S6 .
Figure S6.The mass of water loaded by one IF for different time with or without ultrasound (The actual mass of the loaded liquid was slightly greater than the theoretical value calculated from the porosity because the surface of the IF absorbed a small amount of liquid).

Figure S7 .
Figure S7.Reproducibility experiment of IF loaded with DOX.(a) Mass of DOX loaded by IF with 8 repetitions.(b) RSD of reproducibility experiment of IF loaded with DOX.

Figure S8 .
Figure S8.(a) Schematic diagram for measurement of the release of IF-DOX implant in vitro.(b) The release rate of IF-DOX implant in vitro.

Figure S9 .
Figure S9.(a) Thermal images of IF in AMF under various magnetic field intensities.(b) Heating curves of IF in AMF under various magnetic field intensities.

Figure S10 .
Figure S10.Reproducibility experiment of magnetic heating of IF in an AMF.(a) Temperature change of IF in an AMF with 8 repetitions.(b) RSD of reproducibility experiment of magnetic heating of IF in an AMF.

Figure S12 .
Figure S12.Photos of dissected pig liver coated with pork tissue after treated with PBS or IF in an AMF.

Figure S13 .
Figure S13.Photos of a centrifuge tube filled with thermochromic material (light pink to amaranth at >60°C) and coated in pork tissue after treated with IF or not in an AMF.

Figure S14 .
Figure S14.Schematic diagram of 4T1 cells incubated with IF at the cellular level.

Figure S15 .
Figure S15.The viabilities of 4T1 cells after treating with IF for various time.

Figure S17 .
Figure S17.The Elisa results of IL-6 and TNF-α in serum from mice after implantation of IF for different time.

Figure S18 .
Figure S18.The Elisa results of AFP and CEA in serum from mice after implantation of IF for different time.

Figure S19 .
Figure S19.The degradation rate of IF after implantation in mice for various time.

Figure S21 .
Figure S21.(a) Thermal images of 4T1 tumor-bearing mice with different operations.(b) Heating curves of 4T1 tumor-bearing mice with different operations.(c) Representative photos of 4T1 tumor-bearing mice with various operations for 15 day.(d) Photos of tumors dissected from mice with different treatments on the 15th day.(e) Tumor growth curves of mice after various operations for 15 day.(f) The weight of tumors dissected from mice after different treatments on the 15th day.

Figure S22 .
Figure S22.Residual mass percentage of IF after tumor treatment by IF-DOX implant.