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Near-Infrared-Triggered Nanodroplets for Imaging-Guided Macrophage-Mediated Cancer Immunotherapy
Junxi Yi1,2, Meenakshi Chauhan1,3, Yang Zhao1,2,3,4,5
1Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Small Methods
|July 1, 2025
Summary
This study introduces a laser-activated nanodroplet that reprograms the tumor microenvironment and visualizes treatment response. This innovative approach enhances cancer immunotherapy by targeting tumor-associated macrophages (TAMs) and reducing hypoxia.
Area of Science:
- Oncology
- Biomedical Engineering
- Immunology
Background:
- Solid tumors resist immunotherapy by creating immunosuppressive microenvironments via tumor-associated macrophages (TAMs) and hypoxia.
- Checkpoint blockade therapy efficacy is limited in refractory solid tumors.
- Real-time monitoring of therapeutic response and tumor microenvironment is crucial for adaptive treatment.
Purpose of the Study:
- To develop a laser-triggered theranostic nanodroplet for simultaneous tumor microenvironment remodeling and real-time therapeutic response visualization.
- To investigate the nanodroplet's efficacy in combination with anti-programmed cell death protein 1 (aPD-1) therapy.
- To establish a non-invasive imaging strategy for guiding immunotherapy.
Main Methods:
- Fabrication of double-emulsion perfluorocarbon nanodroplets encapsulating a toll-like receptor-7/8 agonist and indocyanine green dye.
- Laser activation of nanodroplets to generate microbubbles for imaging and drug release.
- In vivo evaluation in a mouse model of triple-negative breast cancer, combining nanodroplets with aPD-1 therapy.
- Dual-modal ultrasound and photoacoustic imaging for longitudinal tracking of biodistribution, macrophage polarization, and oxygen saturation.
Main Results:
- Single nanodroplet injection and laser illumination repolarized M2 TAMs to M1 phenotype, reduced tumor hypoxia, and synergized with aPD-1 therapy.
- A six-fold reduction in tumor size was observed compared to checkpoint blockade alone.
- Non-invasive imaging successfully tracked nanodroplet behavior and tumor microenvironment parameters, enabling real-time treatment guidance.
- Nanodroplets exhibited high loading efficiency (>60%) and good biocompatibility in vitro.
Conclusions:
- The laser-triggered theranostic nanodroplet platform effectively remodels the tumor microenvironment and enables image-guided immunotherapy.
- This approach overcomes key challenges in treating refractory solid tumors, offering a promising strategy for adaptive combination immunotherapy.
- The dual-modal imaging capability provides real-time feedback for optimizing treatment regimens without the need for biopsies.
