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Updated: Oct 11, 2025
Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance
Published on: February 14, 2025
Hypoxia-sensitive drug delivery to tumors
Nina Filipczak1, Ujjwal Joshi2, Sara Aly Attia2
1Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, ul. F. Joliot-Curie 14A, 50-383 Wroclaw, Poland.
Abstract:
Achievement of a high dose of drug in the tumor while minimizing its systemic side effects is one of the important features of an improved drug delivery system. Thus, developing responsive carriers for site-specific delivery of chemotherapeutic agents has become a main goal of research efforts. One of the known hallmarks of cancerous tumors is hypoxia, which offers a target for selective drug delivery. The stimuli-sensitive micellar system developed by us, (PEG-azobenzene-PEI-DOPE (PAPD) has proven to be effective in vitro. The proposed construct developed, PAPD, contains an azobenzene group as a hypoxia-sensitive moiety that triggers the shedding of the PEG layer from the nanoparticle surface under conditions of hypoxia to improve cellular uptake. Using microfluidics, we show significantly improved cellular association and penetration under hypoxia in both single cells and in a 3D tumor model. Employing an in vivo model, we demonstrate slower tumor growth that did not induce systemic side effects, including weight loss in an experimental animal model, when compared to the free drug treatment. This complex-in-nature but simple-in-design system for the simultaneous delivery of siRNA to silence the P-glycoprotein and doxorubicin with active tumor targeting and proven therapeutic efficacy represents a universal platform for the delivery of other hydrophobic chemotherapeutic agents and siRNA molecules which can be further modified.
Insights
A novel hypoxia-sensitive nanoparticle system (PAPD) effectively targets tumors, enhancing drug delivery and reducing side effects. This breakthrough improves chemotherapy efficacy by concentrating medication within cancer cells.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Effective cancer chemotherapy requires high drug concentration in tumors with minimal systemic toxicity.
- Tumor hypoxia is a key characteristic that can be exploited for targeted drug delivery.
- Stimuli-responsive drug delivery systems aim to improve therapeutic outcomes by releasing drugs specifically at the tumor site.
Purpose of the Study:
- To develop and evaluate a hypoxia-sensitive micellar nanoparticle system (PEG-azobenzene-PEI-DOPE, PAPD) for targeted cancer drug delivery.
- To investigate the ability of PAPD to selectively release its payload under hypoxic conditions, enhancing cellular uptake and therapeutic efficacy.
- To assess the in vivo performance of PAPD in reducing tumor growth and systemic side effects.
Main Methods:
- Fabrication of PEG-azobenzene-PEI-DOPE (PAPD) nanoparticles.
- In vitro evaluation of PAPD's stimuli-responsive behavior and cellular uptake using microfluidics in 2D and 3D tumor models under hypoxic conditions.
- In vivo studies using an animal model to assess tumor growth inhibition and systemic toxicity compared to free drug treatment.
Main Results:
- PAPD nanoparticles demonstrated hypoxia-induced PEG layer shedding, leading to enhanced cellular association and penetration in both 2D and 3D tumor models.
- In vivo administration of PAPD resulted in significant tumor growth inhibition without observable systemic side effects, such as weight loss.
- The system successfully co-delivered doxorubicin and siRNA targeting P-glycoprotein, showcasing its potential for combination therapy.
Conclusions:
- The developed PAPD system is an effective hypoxia-targeted drug delivery platform for cancer therapy.
- PAPD offers a promising strategy for improving chemotherapy by enhancing tumor drug accumulation and minimizing systemic toxicity.
- This versatile platform can be adapted for delivering various chemotherapeutic agents and siRNA molecules for enhanced cancer treatment.
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