Abstract
Development of a biomimetic 3D culture system for drug screening is necessary to fully understand the in vivo environment. Previously, a self-assembling peptide hydrogel has been reported; the hydrogel exhibited physiological properties superior to a 3D cell culture matrix. In this work, further research using H9e hydrogel with HeLa cells was carried out considering H9e hydrogel’s interaction with camptothecin, a hydrophobic drug. According to AFM images, a PGworks solution triggered H9e hydrogel fiber aggregation and forms a 3D matrix suitable for cell culture. Dynamic rheological studies showed that camptothecin was encapsulated within the hydrogel network concurrently with peptide self-assembly without permanently destroying the hydrogel’s architecture and remodeling ability. Fluorescence measurement indicated negligible interaction between the fluorophore part of camptothecin and the hydrogel, especially at concentration 0.25 and 0.5 wt%. Using a dialysis method, we found that H9e hydrogel could not significantly inhibit the diffusion of camptothecin encapsulated inside the hydrogel matrix. In the cell culture experiment, HeLa cells were simultaneously embedded in the H9e hydrogel with the initialization of hydrogelation. Most importantly, cell viability data after camptothecin treatment showed responses that were drug-dose dependent but unaffected by the H9e hydrogel concentration, indicating that the hydrogel did not inhibit the drug.
Highlights
The use of the cell-based model is still the main method for in vitro drug efficacy screening to more expediently determine optimal drug dosage in cancer therapy
The fluorescence spectrum, a measure of the average energy of emission, is related to the polarity and flexibility of the polyphenolic side-chain environment[23]. Permana and his coworkers reported that the interaction of camptothecin with carbon nanotubes generated an over- 20 nm shift at most in the fluorescence peak from camptothecin[24]
After treating Hela cells in h9e hydrogel for 3 days with various concentrations of camptothecin, we found a dose-dependent decrease in cell proliferation indicated by the absorbance of 450 nm obtained from CCK-8 assay (Fig. 7) and cell viability (Fig. 8)
Summary
The use of the cell-based model is still the main method for in vitro drug efficacy screening to more expediently determine optimal drug dosage in cancer therapy. Drug diffusion in the 3D hydrogel network is an important factor in drug efficacy screening tests[16]. Some peptide hydrogels possess very strong adhesion to small molecules, making them potential carriers for controlled release[17,18]; for drug efficacy tests in 3D cell cultures, strong affinity between drugs and matrices can have negative effects. The interaction between H9e peptide and drugs must be studied, to ensure h9e hydrogel does not inhibit the effect of drug[19]. We examined the suitability of the peptide hydrogel as a 3D system to evaluate the efficacy of small hydrophobic anticancer drug molecules. A combination of physical and biological analysis proved that h9e hydrogel was a potential promising 3D cell culture for hydrophobic drug camptothecin
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