Abstract: In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.
Abstract: To ensure targeting of apoferritin nanocarrier with
encapsulated doxorubicin drug, we used a peptide linker based on a
protein G with N-terminus affinity towards Fc region of antibodies.
To connect the peptide to the surface of apoferritin, the C-terminus of
peptide was made of cysteine with affinity to gold. The surface of
apoferritin with encapsulated doxorubicin (APODOX) was coated
either with gold nanoparticles (APODOX-Nano) or gold(III) chloride
hydrate reduced with sodium borohydride (APODOX-HAu). The
reduction with sodium borohydride caused a loss of doxorubicin
fluorescent properties and probably accompanied with the loss of its
biological activity. Fluorescent properties of APODOX-Nano were
similar to the unmodified APODOX; therefore it was more suited for
the intended use. To evaluate the specificity of apoferritin modified
with antibodies, ELISA-like method was used with the surface of
microtitration plate wells coated by the antigen (goat anti-human IgG
antibodies). To these wells, the nanocarrier was applied. APODOX
without the modification showed 5× lower affinity to the antigen than
APODOX-Nano modified gold and targeting antibodies (human IgG
antibodies).