pH-titratable superparamagnetic iron oxide for improved nanoparticle accumulation in acidic tumor microenvironments

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Tumorigenesis alters cancer cell metabolism, leading to the Warburg effect.
• The Warburg effect increases glycolysis and lactic acid, creating a low pH tumor microenvironment.
• Targeting this metabolic shift offers a complementary approach to traditional nanoparticle delivery.

Purpose of the Study:

• To design and evaluate pH-responsive iron oxide nanoparticles for enhanced tumor targeting.
• To exploit the acidic tumor microenvironment for improved nanoparticle delivery.
• To develop a T(2)*-weighted MR contrast agent responsive to pH changes.

Main Methods:

• Conjugation of glycol chitosan (GC) to superparamagnetic iron oxide nanoparticles (SPIO).
• In vitro assessment of pH-dependent cellular association and MR contrast.
• In vivo evaluation in murine tumor models using T(2)*-weighted MRI and ICP-MS.

Main Results:

• GC-SPIO nanoparticles demonstrated potent pH-dependent cellular association and MR contrast in vitro.
• In vivo studies showed robust T(2)*-weighted contrast and increased nanoparticle delivery to tumors.
• Enhanced delivery was not solely due to the enhanced permeability and retention (EPR) effect.

Conclusions:

• pH-responsive GC-SPIO nanoparticles effectively target tumors by exploiting the acidic tumor microenvironment.
• This metabolically directed nanoparticle platform offers a promising strategy for cancer diagnosis and therapy.
• The developed nanoparticles provide a novel MR contrast agent with enhanced tumor accumulation.