Development of functional docetaxel nanomicelles for treatment of brain glioma

Abstract

The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm. The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brain glioma-bearing mice. The action mechanisms were associated with dual-modifications by the glucose-lipid derivative and the dequalinium-lipid derivative, both of which are beneficial for the transport across the BBB. Furthermore, the modification with dequalinium-lipid derivative was able to target to the brain glioma cells and to the mitochondria. In conclusion, the functional docetaxel nanomicelles would be a promising formulation for the treatment of brain glioma, deserving further development for clinical trials.

Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p

“…Human malignant gliomas are the most common and lethal primary brain tumor in adults, and glioma cells are featured as carrying heterogeneous genetic molecular aberrations (Ben Abdallah et al, ; Cahill & Turcan, ; Fukami et al, ; Guzman, Edds, Khatua, McGovern, & Robert, ). Irrespective of the applied multimodal therapy including surgical treatment, radiotherapy, and chemotherapy, the survival of patients with glioma is exceptionally poor (Duhamel et al, ; Ju et al, ; Reitman, Winkler, & Elia, ; Scutti, ; C. Wang, Kang, Wang, Liu, & Zhao, ). Henceforth, extensive scrutiny of the molecular mechanisms beneath glioma growth may offer enhanced treatments of gliomas.…”

The potential value of dequalinium chloride in the treatment of cancer: Focus on malignant glioma

“…DQA was more effective than temozolomide (TMZ) at the same concentration and can affect proliferation earlier 7 . DQA‐modified docetaxel nanomicelles can further inhibit glioma cells more effectively than docetaxel nanomicelles 72 . The cytotoxicity of DQA targeting paclitaxel plus artemether liposome was stronger than paclitaxel plus artemether liposome on glioma cells and glioma stem cells 73 …”

The enhanced treatment efficacy of invasive brain glioma by dual-targeted artemether plus paclitaxel micelles

“…The film dispersion method was utilised in preparing dualtargeted artemether plus paclitaxel micelles [17,18]. Briefly, all the materials including PEG 2000 -DSPE, TPGS 1000 , TPGS 1000 -MAN, BK-PEG 2000 -DSPE, artemether and paclitaxel (mass ratio of 37.4:33.6:2.1:4.2:2.1:1) were dissolved in methanol.…”