The lymphatic system plays a critical role in pathological conditions such as lymphedema and chronic inflammation to tumor metastasis, venous insufficiency, and impaired wound healing, making accurate evaluation of its structure and function increasingly important. Yet current imaging tools—including lymphoscintigraphy, magnetic resonance lymphangiography , indocyanine green fluorescence imaging, and conventional methylene blue imaging—often remain limited by invasiveness, poor targeting, high cost, radiation exposure, or insufficient spatial and functional resolution. Although methylene blue is a clinically approved near-infrared dye with a favorable safety profile, it tends to aggregate in water and lacks strong lymphatic specificity because of its very small particle size. Delivering tracers precisely into the dermis also remains a challenge, since standard intradermal injection can be painful and operator-dependent. Based on these challenges, in-depth research is needed to develop safer, more targeted, and more patient-friendly methods for lymphatic imaging.
Researchers from Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, together with collaborators from Shanghai Jiao Tong University and Shanghai Children’s Medical Center,
reported (DOI: 10.1093/burnst/tkaf067) in a 2026 advance article in
Burns & Trauma that a methylene blue nanoparticle delivered through dissolvable microneedles enabled noninvasive near-infrared imaging of lymphatic vessels with higher quality, better targeting, and added functional readouts compared with methylene blue or indocyanine green.
A "Smarter" Tracer
To build the new platform, the team first encapsulated methylene blue in an MPEG-PCL nanocarrier using a double-emulsion method. This design increased particle size from the sub-10 nm range of free methylene blue to about 99 nm, a size better suited for lymphatic uptake. The resulting nanoparticles also shifted to a slightly negative surface charge, showed improved fluorescence, and resisted the quenching and instability that weaken free methylene blue in aqueous solution. In cell studies, the material showed low cytotoxicity, caused less than 5% hemolysis, and was taken up and transported across lymphatic endothelial cells, supporting its promise as a lymphatic imaging tracer.
Painless Delivery
The group then integrated the tracer into dissolvable microneedles arranged in a 15 × 15 array. These microneedles were mechanically strong enough to pierce skin and released about 80% of their payload in vitro, offering a convenient way to place the tracer into the dermis without conventional needle injection. By targeting only the superficial dermal layer, these ultra-fine needles avoid triggering deep-seated pain receptors, ensuring a virtually sensation-free experience for the patient.
Groundbreaking Results
In animal models, the MPEG-PCL@ME platform outperformed current gold standards like indocyanine green and free ME. Key advantages include:
- Superior Clarity: In rats, the platform generated clearer images of lymphatic vessels than methylene blue or indocyanine green at the same concentration. The signal intensity was at least three times higher.
- Precision Targeting: Leakage around the imaging site was minimal, and dominant lymphatic vessels and nodes could be more readily identified.
- Functional Insights: Most notably, the method visualized repeating segmental contractions along lymphatic vessels, making the lymphatic pump easier to recognize and suggesting that the approach can move beyond anatomy to capture functional behavior as well.
“This study turns a familiar clinical dye into a smarter lymphatic probe,” the researchers suggest in essence. By combining nanoscale engineering with dissolvable microneedle delivery, the work addresses several long-standing barriers at once: weak targeting, signal instability, painful administration, and limited ability to assess lymphatic function dynamically. The resulting method is not only easier to use, but also more informative, offering a sharper picture of lymphatic structures and enabling the dynamic assessment of real-time lymph pumping.
The implications could extend well beyond imaging convenience. A portable, painless, and nonradioactive system for lymphatic visualization may support earlier diagnosis of lymphatic dysfunction, better monitoring of lymphedema, and more precise assessment of disease processes linked to impaired lymph flow. Because the tracer also demonstrated satisfactory biosafety in vivo, with no obvious pathological changes in major organs and normal routine blood indices, it may be suitable for longer-term lymphography as the technology develops further. With refinement and clinical translation, this approach could help bring lymphatic imaging closer to bedside practice and make functional lymphatic assessment more accessible in everyday medicine.
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References
DOI
10.1093/burnst/tkaf067
Original Source URL
https://doi.org/10.1093/burnst/tkaf067
Funding Information
This research was supported by the National Natural Science Foundation of China (82172222, 82000456, 82402906), Shanghai Jiao Tong University "Star Project" of Biomedical Multidiscipline Research Program (YG2024ZD13), and SJTU Trans-med Awards Research (NO.WF540162603). All animal experimental procedures were performed according to the Ethical Committee for Animal Experiments of Shanghai Jiao Tong University (China, A2023213).
About Burns & Trauma
Burns & Trauma is an open access, peer-reviewed journal publishing the latest developments in basic, clinical, and translational research related to burns and traumatic injuries, with a special focus on various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, prevention, and regeneration of burns and trauma injury.