Paclitaxel-Ang-2-functionalized bionic mesoporous selenium nanoparticles for targeted therapy of glioma.

in Pharmacological research by Huan Shi, Biaobiao Wang, Zhiwei Shi, Huilin Ma, Yunmei Li, Ying Liu, Yu Zhao, Nan Xia, Chao Wu, Yu Gao

TLDR

  • Researchers designed a nanoparticle, ACMLMSeP, for targeted treatment of glioma through nasal administration, which showed strong targeting capabilities, slowed drug release, and effective anti-glioma activity.

Abstract

Glioma, the most prevalent primary intracranial tumor, presents significant clinical treatment challenges due to its high invasiveness and therapeutic resistance. Therefore, the development of a targeted therapeutic agent that is both highly effective and low in toxicity is crucial. In this research, we aimed to design a bionic mesoporous selenium nanoparticle (ACMLMSeP) functionalized with paclitaxel and Ang-2 for nasal administration as a targeted treatment approach for glioma. Nasal administration facilitates direct delivery of drugs to the brain through the olfactory nerve, thereby circumventing the protective mechanisms of the blood-brain barrier. Mesoporous selenium (MSe) significantly enhances the loading capacity for insoluble drugs while improving their water solubility. The functionalization of MSe enables slow drug release and facilitates targeted drug accumulation. Moreover, accumulated nano-selenium promotes reactive oxygen species (ROS) production, induces autophagy, and synergizes with drugs to accelerate apoptosis in tumor cells. Analysis using Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) indicated that ACMLMSe has an average particle size of roughly 135 nm. Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34 % within 24 h. Cellular uptake studies and in vivo imaging showed the strong targeting capabilities of the ACMLMSeP nanoparticles. Furthermore, the results obtained from the MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations collectively revealed that ACMLMSeP effectively inhibited proliferation while promoting apoptosis in C6 cells. In summary, these experimental findings clearly suggest that ACMLMSeP may serve as a promising biomimetic nanosystem for the targeted treatment of brain glioma.

Overview

  • The study aimed to design a targeted therapeutic agent for glioma using a bionic mesoporous selenium nanoparticle functionalized with paclitaxel and Ang-2 for nasal administration.
  • The nanoparticle, ACMLMSeP, takes advantage of mesoporous selenium to enhance drug loading capacity and water solubility, while also promoting slow drug release and targeted accumulation.
  • The study hypothesized that ACMLMSeP could effectively inhibit glioma cell proliferation and promote apoptosis, potentially serving as a promising biomimetic nanosystem for brain glioma treatment.

Comparative Analysis & Findings

  • The study found that ACMLMSeP exhibited a strong targeting capability for glioma cells, as evident from cellular uptake studies and in vivo imaging
  • Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34% within 24 h
  • The study showed that ACMLMSeP effectively inhibited glioma cell proliferation while promoting apoptosis in C6 cells, as demonstrated by MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations

Implications and Future Directions

  • The study demonstrates the potential of ACMLMSeP as a promising biomimetic nanosystem for targeted treatment of brain glioma, offering a new avenue for overcoming therapeutic resistance and improving patient outcomes
  • Future studies could focus on optimizing ACMLMSeP's formulation, assessing its efficacy in various glioma models, and exploring its potential for combination therapy with other treatments
  • The study's findings highlight the need for further investigation into the molecular mechanisms underlying ACMLMSeP's anti-glioma activity, with the aim of identifying potential biomarkers for treatment monitoring and patient selection
Read Full Article