Drug Res (Stuttg) 2020; 70(02/03): 71-79
DOI: 10.1055/a-1016-6889
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Preparation and Characterization of Albumin Nanoparticles of Paclitaxel-Triphenylphosphonium Conjugates: New Approach to Subcellular Targeting

Nastaran Hosseinifar
1  Department of Applied Chemistry, Faculty of Chemistry, Islamic Azad University Tehran-North Branch, Iran
,
Navid Goodarzi
2  Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
Amir Abdolah Mehrdad Sharif
3  Department of Analytical Chemistry, Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran
,
Mohsen Amini
4  Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
Mehdi Esfandyari-Manesh
2  Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
Rassoul Dinarvand
2  Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
› Author Affiliations
The financial support of this work from Iran National Science Foundation (INSF) under Grant No. 92030820.
Further Information

Publication History

received 08 July 2019
revised

accepted 19 September 2019

Publication Date:
27 January 2020 (online)

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.