Abstract
In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development.
Highlights
GCPQ micelles show a moderate toxicity without the cargo, which could be attributed to their strong cationic nature
Experiments on tumoroids show that the efficacy of large cationic nanoparticles is limited due to a poor diffusion through the cancer mass
These results illustrate the efficacy of cationic organic nanocarriers for hydrophobic drug delivery and highlight the importance of accounting for the tumor microenvironment during drug development, in the case of nanoformulations
Summary
We use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model
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