Assessment of an Integrative Anticancer Treatment Using an in Vitro Perfusion-Enabled 3D Breast Tumor Model

Abstract

The study presents observations on anticancer therapeutic efficacy of magnetic fluid hyperthermia and a combination of hyperthermia and chemotherapy (i.e., integrative treatment) using an in vitro perfused and non-perfused 3D breast tumor model. The 3D in vitro breast tumor models were simulated using Comsol multiphysics, fabricated using specially designed chips, and treated with doxorubicin-loaded chitosan-coated La0.7Sr0.3MnO3 (DC-LSMO) nanoparticles for hyperthermia and combination therapy in both perfused and non-perfused conditions. Computation confirmed uniform heat distribution throughout the scaffold for both the models. The findings indicate that both hyperthermia and combination treatment could trigger apoptotic cell death in the perfused and non-perfused models in varying degrees. Specifically, the perfused tumors were more resistant to therapy than the non-perfused ones. The efficacy of anticancer treatment decreased with increasing physiological complexity of the tumor model. The combination (hyperthermia and chemotherapy) treatment showed enhanced efficacy over hyperthermia alone. This is a pilot study to investigate the effects of magnetic fluid hyperthermia–chemotherapy treatment using perfused and non-perfused 3D in vitro models of tumor. The feasibility of using 3D cell culture models for contributing to our understanding of cancer and its treatment was also determined as a part of this work.

Functionalized manganese iron oxide nanoparticles: a dual potential magneto-chemotherapeutic cargo in a 3D breast cancer model

“…Despite being loaded onto chitosan-coated MIONPs, doxorubicin still has a charge higher than negatively or neutrally charged molecules, suggesting that it may be passing the cell membrane. 36 We looked at how well chemotherapy and thermotherapy worked together (due to DOX). In a previous section, the continuous release of DOX from DOX@CS–MIONPs on the MCF7 cell line was demonstrated (Fig.…”

“…However, how cells engage with 3D-structured nanomaterials in a genuine tissue milieu cannot be fully understood using a 2D culture setup. 36 MCF7 cell lines were used to assess the CS-MIONPs biocompatibility and cytotoxicity. The cytotoxicity of CS-MIONPs was assessed by incubating the cells with varying dosages of nanoparticles (10,25,50,100,200, and 400 µg mL −1 ) and compositions (i.e., CS-MIONPs, DOX@CS-MIONPs and nanocarrier, i.e., Apt@DOX@CS-MIONPs) at 24 h. As mentioned above, the MTT assay was utilized to determine the cell viability, revealing no apparent toxicity of CS-MIONPs when incubated with cells at the appropriate concentrations.…”

Engineering Breast Cancer Microenvironments and 3D Bioprinting

“…The perfused spheroids displayed increased resistance to both the hyperthermia and combination therapies when compared to the spheroids cultured on the same scaffold, but not perfused. This increased resistance to therapy indicates the importance of constant perfusion in tumors (Kulkarni et al, 2018 ).…”