Liquid crystalline lipid nanoparticles for combined delivery of curcumin, fish oil and BDNF: In vitro neuroprotective potential in a cellular model of tunicamycin-induced endoplasmic reticulum stress

被引：0
作者：
Rakotoarisoa M. [1 ]
Angelov B. [2 ]
Drechsler M. [3 ]
Nicolas V. [4 ]
Bizien T. [5 ]
Gorshkova Y.E. [6 ]
Deng Y. [7 ]
Angelova A. [1 ]
机构：
[1] Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Châtenay-Malabry
[2] Institute of Physics, ELI Beamlines, Academy of Sciences of the Czech Republic, Na Slovance 2, Prague
[3] Keylab “Electron and Optical Microscopy”, Bavarian Polymerinstitute (BPI), University of Bayreuth, Universitätsstrasse 30, Bayreuth
[4] UMS-IPSIT MIPSIT, Université Paris-Saclay, Inserm, CNRS, Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT)
[5] Synchrotron SOLEIL, l'Orme des Merisiers, Saint-Aubin - BP 48, Gif-sur-Yvette Cedex
[6] Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie Str. 6, Dubna
[7] Wenzhou Institute, University of Chinese Academy of Sciences, No.1, Jinlian Road, Longwan District, Zhejiang, Wenzhou
来源：
Smart Materials in Medicine | 2022年 / 3卷
基金：
中国国家自然科学基金;
关键词：
Brain-derived neurotrophic factor (BDNF); Cryo-TEM; Cubosome; Curcumin; Endoplasmic reticulum stress; Lipid liquid crystalline nanoparticles; Nanomedicine; Neuroprotection; SAXS; Spongosome; Tunicamycin;
D O I：
10.1016/j.smaim.2022.03.001
中图分类号：
学科分类号：
摘要：
We develop multidrug-loaded cubosome and spongosome lipid nanoparticles for targeting of endoplasmic reticulum stress as a potential emerging therapeutic strategy against neuronal degeneration. The multicompartment organization of the liquid crystalline nanoparticles (LCNPs), fabricated by self-assembly, was characterized by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Monoolein-based cubosome and spongosome LCNPs co-encapsulated the natural plant-derived antioxidant curcumin, fish oil rich in ω-3 polyunsaturated fatty acids (PUFA), and the neurotrophin brain-derived neurotrophic factor (BDNF), which is of vital need for neurogenesis. The neuroprotective properties of the nanoparticles were in vitro investigated in a cellular model of tunicamycin-induced endoplasmic reticulum (ER) stress using differentiated human neuroblastoma SH-SY5Y cells deprieved from serum. The intracellular accumulation of aggregates of misfolded proteins, typical for the ER stress process, was analyzed by fluorescence microscopy co-localization imaging and ER staining. The performed cellular bioassays established that the BDNF-loaded LCNPs enhanced the neuronal cell survival. The diminution of the tunicamycin-induced ER stress upon internalization of neuroprotective nanoparticles was quantified via the changes in the Thioflavin T fluorescence, which is a sensitive marker of protein aggregation. LCNPs with multi-drug loading appear to be promising candidates to face the challenges in neuroprotective nanomedicine development by exploiting ER-stress targeting mechanisms. © 2022 The Authors
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页码：274 / 288
页数：14
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