Metformin loaded MnO@SiOcore-shell nanoparticles for glioblastoma multiforme targeted therapy.

in Colloids and surfaces. B, Biointerfaces by Zahra Nozhat, Abdul Wahab, Asim Mushtaq, M Zubair Iqbal, Xiangdong Kong

TLDR

  • The study developed metformin-loaded nanoparticles that effectively targeted and treated glioblastoma cells, showing potential for improved treatment outcomes.
  • The nanoparticles demonstrated enhanced drug delivery and pH-responsive release, outperforming free metformin in reducing cell viability and inhibiting cell migration.
  • The study establishes a foundation for developing manganese-based nanomedicines for precise cancer therapy

Abstract

Glioblastoma multiforme (GBM) presents unique challenges that contribute to a poor early-stage prognosis, primarily due to the difficulty of chemotherapy drugs face in crossing the blood-brain barrier (BBB). Despite decades of research, overall survival rates for GBM patients remain low. However, modified nanoscale biomaterials show promise in enhancing drug delivery and efficacy by effectively penetrating the BBB. In this study, we developed metformin (MET)-loaded Mn₃O₄@SiO₂@cRGD nanoparticles (MSMC NPs) as a targeted pH-responsive drug delivery system for treating glioblastoma (GBM). The nanoparticles demonstrated a high drug-loading capacity of 69.4 ± 3.7 % and an encapsulation efficiency of 11.5 ± 2.1 %. In vitro studies showed that MSMC NPs significantly enhanced cellular uptake in U251 and U87 GBM cells, with a 2.5-fold increase in fluorescence intensity compared to non-targeted nanoparticles. The pH-responsive release of MET reached 70 % at pH 5.5, compared to only 30 % at pH 7.4 over 48 hours. MSMC NPs resulted in a 55.6 % reduction in U251 cell viability and a 43.4 % decrease in U87 cell viability at a 15 mM MET concentration, significantly outperforming free MET. Furthermore, the nanoparticles inhibited cell migration by 80 % in a 3D spheroid model and increased apoptosis rates by 40 % in U251 cells and 35 % in U87 cells. These findings highlight the potential of MSMC NPs as a targeted, pH-responsive, and theranostic platform for improving GBM treatment by enhancing drug delivery and minimizing off-target effects. This study establishes a foundation for developing Mn₃O₄-based nanomedicines for precise cancer therapy.

Overview

  • The study developed metformin-loaded Mn₃O₄@SiO₂@cRGD nanoparticles (MSMC NPs) for targeted, pH-responsive drug delivery in treating glioblastoma (GBM).
  • The nanoparticles demonstrated high drug-loading capacity and encapsulation efficiency, and exhibited pH-responsive release of metformin.
  • The primary objective of the study was to investigate the potential of MSMC NPs as a targeted, pH-responsive, and theranostic platform for improving GBM treatment.

Comparative Analysis & Findings

  • MSMC NPs significantly enhanced cellular uptake in U251 and U87 GBM cells, with a 2.5-fold increase in fluorescence intensity compared to non-targeted nanoparticles.
  • The pH-responsive release of metformin from MSMC NPs was 70% at pH 5.5, compared to only 30% at pH 7.4 over 48 hours.
  • MSMC NPs resulted in a 55.6% reduction in U251 cell viability and a 43.4% decrease in U87 cell viability at a 15mM metformin concentration, significantly outperforming free metformin

Implications and Future Directions

  • The study highlights the potential of MSMC NPs as a targeted, pH-responsive, and theranostic platform for improving GBM treatment by enhancing drug delivery and minimizing off-target effects.
  • Future studies can focus on investigating the safety and efficacy of MSMC NPs in animal models and human clinical trials.
  • The development of Mn₃O₄-based nanomedicines for precise cancer therapy is established as a foundation for future research
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