Folate-PEG3-alkyne

Mo J, et al. Scientific Reports, 2016, 6, 23489.

Folate-PEG3-alkyne is an azide linker that can modify the surface of phosphonated calix[4]arene vesicles (PCV) via a click reaction to provide a targeted delivery system for the potent but toxic drug paclitaxel (PTX).
The binding of folic acid (FA) to the membrane folate receptor (FR) initiates FA internalization and any drug delivery platforms that strategically bind to FA. Subsequent isolation of the contents into acidic endosomes ensures that this approach not only enables cancer-directed drug delivery but also has the potential to enhance cellular uptake of the delivered drug.
Polyethylene glycol is added as a spacer between the FA and the vesicle surface to enhance aqueous solubility, optimize the targeting activity of the surface-attached FA, and increase the potential to prolong the systemic half-life of the vesicles.
fP-PCV is prepared as follows:
1.Combine equimolar amounts of alkyne-PEG-folic acid reagent and azide-functionalized PCVPTX (P3C6N3).
2.Add CuSO⁴ and sodium ascorbate to the mixture to catalyze the "click" reaction.
Reaction conditions are determined:
Fourier transform infrared spectroscopy (FTIR) is performed to monitor the progress of the reaction.
Verify the disappearance of azide absorption at 2122 cm^-1 and alkyne absorption at 3333 cm^-1.
Confirmation of triazole ring formation with a new absorption band at 3136 cm^-1 indicates successful binding of PEG-folic acid to the vacuolar molecules within the vesicles.
Expected results and caveats:
The reaction efficiency is expected to be about 50% due to the inner and outer surfaces of the vesicles.
It is hypothesized that the destruction of the vacuolar molecules between the outer and inner layers of the vesicle bilayer requires mechanical energy input, similar to the treatment of vesicles using a thin film vortex fluidic device.