Dual chemotherapy-chemodynamic hybrid lipid-iron nanoparticles for enhanced glioblastoma therapy

This poster has been presented at the  15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology  which took place in Prague, Czech Republic.

Dual chemotherapy-chemodynamic hybrid lipid-iron nanoparticles for enhanced glioblastoma therapy

Introduction

Glioblastoma (GBM) , the most aggressive primary brain cancer, presents significant challenges in treatment due to its resistance to conventional therapies, high recurrence rates, and complex tumor heterogeneity. The development of targeted hybrid nanoparticles (HNPs) emerge as a novel approach to enhance GBM treatment. The HNPs comprise celecoxib (CXB)-loaded nano strutured lipid carriers (NLCs) as a chemotherapeutic strategy and iron oxide nanoparticles (IONPs), which served as a mediator for chemodynamic therapy (CDT). Additionally, the covalent attachment of Apolipoprotein E (ApoE) peptide is hypothesized to enhance therapeutic efficacy and to impart specific targeting properties to breach the blood-brain barrier (BBB) [1,2].

Innovative therapeutic approaches are needed!

Hybrid nanoparticles combine inorganic (iron oxide) and organic (nanostructured lipid carriers) nanoparticles to harness novel and valuable capabilities.

How is the strategy implemented?

Methods

Physicochemical characterization

HNPs production

Aqueous surfactant phase
• Tween®80 (4.2% w/w)
Lipid phase
• Precirol®ATO 5: Oleic acid (75:25, at 7.5% w/w)
• CXB (3%, considering the lipid content)
• IONPs (20% v/v)

Surface functionalization

In vitro studies

Cellular line: U87-MG cells (Human glioblastoma)

In vivo performance

Biodistribution studies

Administration: Intravenous
Quantification: HPLC

Dose: 10 mg/kg
Time-points: 10, 20, 30, 60, 90, 180 and 240 min.

Efficacy studies

Results and discussion

Physicochemical characterization

Table1. Colloidal properties of IONPs, HNPs-CXB, HNPs-ST and HNPs-CXBAPOE. Key: PS-Particle size; PDI-Polydispersity index; ZP-Zeta potential; CV-Coefficient of variation. The results are expressed as mean ±SD (n=9).

The PS of HNPs-CXBApoE was around 107 nm, the PDI average sat 0.273, indicating narrow distribution, and the ZP was -42mV, suggesting good colloidal stability, as demonstrated in Table 1.
The addition of ApoE, as active targeting to U87 cells, did not change the colloidal properties significantly.

In vitro studies

Cellular uptake

Figure 1. Cellular uptake in U87 (down) of HNPs-CXBApoE formulations after 0.5h, 1h and 2h of incubation. Green (C6), blue (DAPI) and red (Alexa-Fluor 594)

Reactive oxygen species (ROS) production

Figure 2. Intracellular ROS generation induced by IONPs and HNPsApoEafter 2 h and 24 h of incubation. Values presented the mean±SD (n=9).

The catalytic properties of HNPs-CXBApoEfacilitated the conversion of endogenous hydrogen peroxide (H2O2), mainly at 2h, into highly reactive hydroxyl radicals, inducing oxidative stress within U87 cells.

BBB permeability

TEER did not change through the 4 hours of the study. Cell viability after 4 hours was 100%.

Surface-functionalized HNPs exhibited 1.60-fold higher permeability compared to non-functionalized HNPs

Figure 3. Confocal images to evaluate the distribution of HNPs through the 2D-BBB model in HBMEC (apical side) and U87 cells (bottom of the plate). Green (C6) represents the nanoparticle internalization through the 2D-BBB model, and blue represents signals from the nucleos (DAPI).

See the full poster on Dual chemotherapy-chemodynamic hybrid lipid-iron nanoparticles for enhanced glioblastoma therapy here

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Authors: Maria Mendes, Patrícia Rasteiro, Joel Barcelos, José Sereno, João José Sousa, Alberto Pais, Carla Vitorino, University of Coimbra, Portugal, Coimbra Chemistry Centre,Net4Brain, poster: Dual chemotherapy-chemodynamic hybrid lipid-iron nanoparticles for enhanced glioblastoma therapy

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