Improved Delivery Performance of n-Butylidenephthalide-Polyethylene Glycol-Gold Nanoparticles Efficient for Enhanced Anti-Cancer Activity in Brain Tumor

n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:11
Enthalten in:	Cells - 11(2022), 14 vom: 11. Juli

Sprache:	Englisch

Beteiligte Personen:	Hsing, Ming-Tai [VerfasserIn] Hsu, Hui-Ting [VerfasserIn] Chang, Chih-Hsuan [VerfasserIn] Chang, Kai-Bo [VerfasserIn] Cheng, Chun-Yuan [VerfasserIn] Lee, Jae-Hwan [VerfasserIn] Huang, Chien-Li [VerfasserIn] Yang, Meng-Yin [VerfasserIn] Yang, Yi-Chin [VerfasserIn] Liu, Szu-Yuan [VerfasserIn] Yen, Chun-Ming [VerfasserIn] Yang, Shun-Fa [VerfasserIn] Hung, Huey-Shan [VerfasserIn]

Links:	Volltext

Themen:	3WJQ0SDW1A 7440-57-5 Anti-cancer capacity Apoptosis Regulatory Proteins Butylidenephthalide DBTRG human glioblastoma multiforme Gold Gold nanoparticle Journal Article N-butylidenephthalide Phthalic Anhydrides Polyethylene Glycols Polyethylene glycol Research Support, Non-U.S. Gov't S9178G4B3F

Anmerkungen:	Date Completed 28.07.2022 Date Revised 06.11.2022 published: Electronic Citation Status MEDLINE

doi:	10.3390/cells11142172

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM344034062