Synergistic inhibition of human glioma cell line by temozolomide and PAMAM‐mediated miR‐21i

Abstract

Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly and with a high frequency. Efforts to overcome chemoresistance are, therefore, critically needed. In present study, a poly(amidoamine; PAMAM) dendrimer was used as a vector to deliver microRNA-21 inhibitor (miR-21i) into U87 cells and the chemosensitivity of the combination effect of miR-21i and TMZ for glioma therapy was investigated. Flow cytometry analysis showed the uptake efficiency of microRNA-21 inhibitor after complexation with PAMAM. Real-time PCR and in situ hybridization indicated that, compared with TMZ or miR-21i treated cells, cells simultaneously treated with miR-21i and TMZ showed a remarkable decrease in the microRNA-21 (miR-21) level. The transfection of miR-21i enhanced the chemosensitivity by significantly decreasing the IC50 value of TMZ to glioma cells. Knockdown of miR-21 promoted the cells' apoptosis, and at the same time, inhibited cell invasion. In conclusion, the combination treatment of glioma cells with TMZ and miR-21i could yield a synergistic effect in inhibition of human glioma cell line.

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment

“…In addition, therapy based on cells ( Sharma et al, 2020 ; Wang et al, 2020 ) (CAR T cell, tumor-associated macrophage) and oncolytic virus 2018; Yoo et al (2019) provides an innovative idea for the treatment of GBM and bridging the gap between clinical needs and effective treatment. The combination of chemotherapy, radiotherapy, gene therapy, and monoclonal antibody, and so on ( Qian et al, 2013 ; Shi et al, 2013 ; Qian et al, 2014 ; Ren et al, 2014 ; Meng et al, 2016a ; Meng et al, 2016b ; Qi et al, 2016 ; Ren et al, 2016 ; Ashton et al, 2018 ; Desjardins et al, 2018 ; Jia et al, 2018 ; Zhao et al, 2018 ; Liu et al, 2019a ; Qian et al, 2019 ; Zhan et al, 2020 ; Qi et al, 2021 )can reduce the systemic dosage and related side effects, broaden the treatment window, and rejuvenate some candidate drugs that are on the verge of failure. Certainly, combination therapy is not just a simple combination of several methods, a lot of preclinical researches must be performed to find suitable drugs, medication time points and the treatment sequence.…”

Tailoring drug and gene codelivery nanosystems for glioblastoma treatment

“…Poly(amidoamine) (PAMAM) dendrimers, the most important dendrimer type, have been used as miRNA delivery systems applied to GBM treatment with promising preclinical outcomes (Qian et al, 2013. Thus, miR-7/FA-PAMAM polyplexes were developed and in vitro treatment of U251 glioma cells with these miRNA complexed formulations exhibited higher transfection efficiency compared to miR-7/liposomes group.…”

“…Moreover, the proposed nanosystem displayed an interesting role in sensitization of glioma cells to TMZ, improving therapy efficacy (Figure 8.3) (Ananta et al, 2016). AntimiR-21/poly(amidoamine) (PAMAM) polyplexes also showed promising results in decreasing the expression of miR-21 when combined with TMZ treatment and, consequently, enhancing the chemosensitivity of U-87 MG cells to TMZ treatment (Qian et al, 2013).…”

Polymer nanocarriers for MicroRNA delivery

“…When complexed with biological molecules, dendrimers are called dendriplexes, and cationic dendrimers are a practical choice of carrier for miRNA because they can readily associate with negatively charged nucleic acids. While many dendrimer types have been explored for siRNA delivery and antagomiR delivery, little research has examined the use of dendrimers for miRNA mimic delivery. Below, we describe some of the findings in this field to date.…”