Abstract
Mitochondria have been recognized as important targets in cancer therapy due to their
role in the respiratory process of cells. One approach employed for mitochondrion
targeting is conjugation of a delocalized cation such as triphenylphosphonium (TPP),
with antineoplastic agents, for instance paclitaxel (PTX). In cell cytoplasm, TPP-PTX
can come close to mitochondria due to its high positive charge, which has a strong
tendency toward the enhanced negative charge of mitochondria. The esteric bond of
TPP-PTX can break down in the acidic environment of tumor cells and release the PTX,
which can act directly on mitochondria to kill tumor cells. TPP-PTX was synthesized
in three steps: Succinic anhydride (SUC) reacted with PTX to achieve succinyl paclitaxel
(SUC-PTX), which has an acid-labile esteric bond. Then 2-triphenylphosphonium ethylammonium
(ATPP) was prepared by attaching 2-bromoethylammunium bromide to TPP. Finally, a TPP-PTX
prodrug was synthesized by attaching these materials. The products of all steps were
characterized by thin-layer chromatography (TLC), infrared spectroscopy (IR), and
nuclear magnetic resonance (1H NMR, 13C NMR). The purity of the products was determined by HPLC methods. TPP-PTX, as a prodrug,
was loaded in to human serum albumin (HSA) nanoparticles by a method inspired by nab-technology
with 130–160 nm particle size distribution, PdI=0.166 and Zeta potential −12.6 mV.
Key words
paclitaxel - triphenylphosphonium - human serum albumin - EPR effect - targeted delivery
- nanoparticles
