Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles

Abstract

Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano-biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles-from self-assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.

Water‐Responsive Hybrid Nanoparticles Codelivering ICG and DOX Effectively Treat Breast Cancer via Hyperthermia‐aided DOX Functionality and Drug Penetration

“…To evaluate the tumor penetration capability of PL/ACC‐DOX&ICG, we established 4T1 MCTS to mimic an in vivo solid tumor. Compared with the 2D cell model cultured in monolayers, MCTS have been employed as a 3D cell model in vitro to study tumor biology and the therapeutic efficacy of various therapies . Moreover, MCTS can simulate the microenvironment of the tumor by recapitulating physiological cell–cell and cell–ECM interactions.…”

Biodegradable Periodic Mesoporous Organosilica (BPMO) Loaded with Daunorubicin: A Promising Nanoparticle‐Based Anticancer Drug

“…This model reproduces a three dimensional (3D) avascular multicellular tumor. It is a promising method for the evaluation of tumor penetration and cytotoxicity of drug nanoformulations . Green fluorescent protein (GFP) expressing human ovarian cancer cells (OVCAR8) were grown on a spheroid forming plate for 7 days to generate tumor spheroids.…”

“…It is a promising method for the evaluation of tumor penetration and cytotoxicity of drug nanoformulations. [22,[36][37] Green fluorescent protein (GFP) expressing human ovarian cancer cells (OVCAR8) were grown on a spheroid forming plate for 7 days to generate tumor spheroids. Spherical mass of cancer cells was produced as shown in Figure 3.…”

A simple microsphere‐based mold to rapidly fabricate microwell arrays for multisize 3D tumor culture

“…To further demonstrate the practical application of the microwell arrays, uniformly sized 3D tumors were selectively generated in a 400 μm concave microwell arrays and used for on‐chip drug cytotoxicity assay. DOX was used as a model anticancer drug because it provides better activity on solid tumors (Lu & Stenzel, 2018). After HepG2 tumors were formed in the concave microwell arrays, they were subsequently treated by six different concentrations of DOX (0.05, 0.2, 1.0, 5.0, 25, and 100 μg/ml) for 1 day.…”