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. 2021 Oct 1;11:19539. doi: 10.1038/s41598-021-98554-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Temporal distribution of drug at different compartments during ThermoDox-mediated delivery; Increasing the injected dose of ThermoDox enhances the concentration of therapeutic agents at each stage $(I = 0.0191 \frac{kg}{m^{3}}, 2 I = 0.0382 \frac{kg}{m^{3}}, 3 I = 0.0573 \frac{kg}{m^{3}})$ . The concentration of free and bound drugs in the capillary network is more than twice that of systemic plasma, which rapidly crosses the vessel wall and enters the tumor interstitium. The bound drug has similar variation with the free drug, but nearly three times greater. Concentration in intracellular compartment could have more drug due to the high extracellular concentration of drug.