Micelles and vesicles have long been proposed as carriers for low molecular weight molecules including drugs. The ability of micelles to deliver drug is usually tested by incubating them with a monolayer of cell. This assay does not take the actual structure of tumors into account, since it neglects the necessary penetration of particles into the tissue. Multicellular tumor spheroids (MCTS) can act as a 3D tumor model to investigate the biological responses to polymeric micelles.
Therefore, a range of nanoparticles were prepared to study the correlation between nanoparticle type and spheroid penetration. It was found that MCT are not only closer in design to in vivo models than traditional 2D models, but they provide more information on the ability of nanoparticles to deliver drugs. For example, drugs such as paclitaxel, conjugated to polymeric drug carriers, show a significantly decreased in vitro activity as the drug needs to be cleaved from the carrier in order to be active. However, MCTs that do also look at penetration of nanoparticles across the micrometer length scale can show that the polymer drug conjugate may indeed be superior to the free drug. Stable micelles, which were stabilized by crosslinking, penetrated deeper and delivered more drugs into MCTS than the diffusion of the free drug. It was found that the micellar penetration depended more on transcellular transport than on diffusion through extracellular matrices.
In this work, we will discuss various drug delivery carriers and investigate their performance in MCTS. In particular we will discuss nanoparticles that are based on synthtic polymers combined with natural building blocks such as sugars or proteins. For example, we have adopted a new strategy by employing polymer-albumin conjugates. The attached polymer determines the interaction with the drug allowing fine-tuning the system for any drug delivery problem. This technique was tested on hydrophobic drugs, metal-based drugs and nucleic acid drugs. In this presentation, we will discuss conjugation strategies between polymer and albumin and the self-assembly process into nanoparticles. These nanoparticles are loaded with various drugs and tested using various cancer cell lines.