Trivalent Gadolinium Ions Forming Injectable Hydrogels for Simultaneous In Situ Vaccination Therapy and Imaging of...

Area of Science:

• Biomedical Engineering
• Oncology
• Materials Science

Background:

• Doxorubicin (DOX) is a first-line treatment for soft tissue sarcomas (STS), but its clinical use is limited by dose-dependent toxicity.
• Doxorubicin can induce immunogenic cell death (ICD), presenting an opportunity for immunotherapy strategies like "in situ vaccination".

Purpose of the Study:

• To develop a visualized, in situ forming hydrogel platform for sustained local delivery of DOX and PD-1 inhibitors for STS treatment.
• To evaluate the efficacy of this "in situ vaccination" strategy in preclinical STS models.

Main Methods:

• A hyaluronic acid-dopamine (HA-DOPA) hydrogel was synthesized and coordinated with gadolinium ions (Gd3+).
• Gd3+ enabled magnetic resonance imaging (MRI) for in vivo tracking and hydrogel cross-linking.
• The hydrogel platform was tested in mouse STS models for sustained drug release, tumor growth inhibition, and immune response modulation.

Main Results:

• The HA-DOPA/Gd3+ hydrogel demonstrated sustained release and effective in vivo imaging tracking.
• The "in situ vaccination" hydrogel significantly inhibited tumor growth in mouse STS models.
• Treatment increased T cell infiltration, promoted M1 macrophage polarization, and counteracted DOX-induced PD-1/PD-L1 upregulation.

Conclusions:

• The developed injectable hydrogel platform shows promise for localized STS treatment via "in situ vaccination".
• This platform facilitates sustained drug delivery, real-time monitoring, and enhanced antitumor immune responses.
• The findings suggest a potential universal platform for "in situ vaccination" strategies in STS therapy.