Induction Therapy of Retinoic Acid with a Temozolomide-Loaded Gold Nanoparticle-Associated Ultrasound Effect on Glioblastoma Cancer Stem-Like Colonies
Journal
ACS Applied Materials and Interfaces
Journal Volume
13
Journal Issue
28
Pages
32845-32855
Date Issued
2021
Author(s)
Abstract
Glioblastoma multiforme (GBM) is the most aggressive glioma. The treatment response is always low, and the condition is typically rapidly fatal. The undifferentiated and self-renewal characteristics of cancer stem cells (CSCs) have been reported, and their potential contribution may cause tumor initiation, recurrence, metastasis, and therapeutic resistance. In particular, glioblastoma stem-like cells exhibit highly invasive properties and drug resistance, serving as a model for the development of novel therapeutic strategies. Induction therapy provides an alternative therapeutic strategy to eliminate the stem cell properties of CSCs and enhance therapeutic sensitivity. The differentiated cells may lose their self-renewal ability, downregulate stem cell-related genes and drug resistance genes, and enhance anticancer drug sensitivity. Therefore, the purpose of this study is to establish a niche for glioblastoma stem-like cell selection as a platform and facilitate the assessment of differentiation therapy on GBM cancer stem-like colonies by retinoic acid (RA) with temozolomide (TMZ)-loaded gold nanoparticles (GNPs) associated with low-intensity ultrasound (LIUS). Herein, a hyaluronic acid-based material system was used to isolate GBM cancer stem-like colonies. Colony formation, size determination, stem cell-related marker expression, and GBM cancer stem-like cell marker expression with the culture period were identified. The effect of TMZ on GBM stem-like colonies on HA-based material systems was also determined, and the results revealed that drug resistance was highly enhanced in GBM colonies compared with that in the control cell population. In addition, GBM colonies also exhibited a significant increase in breast cancer resistance protein expression, which is consistent with the drug resistance effect. Furthermore, several factors, including LIUS, RA, and GNPs, were used to determine the possibility of induction therapy. RA with TMZ-loaded GNP-associated LIUS stimulation exhibited a significant and synergistic effect on the differentiation effect and drug sensitivity enhancement. The GBM cancer stem-like colony system presents an opportunity for the development of new therapeutic strategies, and this study provides an alternative differentiation therapy for malignant tumors. ? 2021 American Chemical Society.
Subjects
drug resistance
glioblastoma cancer stem-like colony
induction therapy
low-intensity ultrasound
retinoic acid
TMZ-loaded gold nanoparticles
Cell culture
Cell proliferation
Diseases
Genes
Gold nanoparticles
Hyaluronic acid
Metal nanoparticles
Planning
Stem cells
Tumors
Ultrasonics
Breast cancer resistance proteins
Differentiated cells
Drug resistance genes
Glioblastoma multiforme
Gold nanoparticles (GNPs)
Low intensity ultrasound
Synergistic effect
Therapeutic strategy
Drug delivery
antineoplastic agent
drug carrier
gold
hyaluronic acid
metal nanoparticle
temozolomide
cancer stem cell
cell differentiation
chemistry
drug effect
drug potentiation
drug release
glioblastoma
human
induction chemotherapy
multicellular spheroid
tumor cell line
ultrasound
Antineoplastic Agents
Cell Differentiation
Cell Line, Tumor
Drug Carriers
Drug Liberation
Drug Resistance, Neoplasm
Drug Synergism
Glioblastoma
Gold
Humans
Hyaluronic Acid
Induction Chemotherapy
Metal Nanoparticles
Neoplastic Stem Cells
Spheroids, Cellular
Temozolomide
Tretinoin
Ultrasonic Waves
SDGs
Type
journal article