Elucidating the mechanism of cellular uptake
We also assess the potential of poly(butyl cyanoacrylate) (PBCA) and poly(octyl cyanoacrylate) (POCA) nanoparticles for intracellular drug delivery in the prostate cancer cell line PC3 and rat brain endothelial cell line RBE4 and the role of endocytosis pathways in PACA nanoparticle uptake in those cell lines.
Fluorescence lifetime imaging, emission spectra analysis and Förster resonance energy transfer indicated that the intracellular degradation was in line with the degradation found by direct methods such as gas chromatography and scanning electron microscopy, showing that PBCA has a faster degradation rate compared to POCA.
This indicates that it is possible to tune the intracellular drug release rate by choosing appropriate monomers from the PACA family or by using hybrid PACA nanoparticles containing different monomers.
In addition, we showed that the uptake of PACA nanoparticles depends not only on the monomer material, but also on the cell type, and that different cell lines can use different internalization pathways. One strategy is to encapsulate drugs into nanoparticles (NPs).
The three complementary optical techniques showed that the intracellular degradation rates of the PBCA and POCA NPs are in line with the rates measured in solution.
Endocytosis is an energy-dependent process and is strongly inhibited at low temperatures [ The effect of inhibition of endocytosis by genistein and chlorpromazine on the uptake of PBCA and POCA NPs in a PC3 cells and b in RBE4 cells. The median fluorescence intensity is expressed relative to autofluorescence.
The uptake of NPs in cells, including PACA NPs, demonstrates different uptake efficacy by different cell types and organs , but knowledge of the intracellular degradation of different PACA NPs remains scarce.
Thus, the aim of our work was to study the cellular uptake of PACA NPs and their intracellular degradation, leading to the release of a model drug.
Their advantages include easy fabrication and functionalization, biocompatibility, sustained drug release and controllable degradation rate .
These particles can be made from different alkyl cyanoacrylate monomers and their mixtures, leading to varying degradability.