Bivalent Gadolinium Ions Forming Injectable Hydrogels for Simultaneous In Situ Vaccination Therapy and Imaging of
Chun Wang1,2, Yuanhao Jing3, Wenting Yu4
1The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Abstract:
Doxorubicin (DOX) is the classic soft tissue sarcomas (STS) first-line treatment drug, while dose-dependent myelosuppression and cardiotoxicity limit its application in clinic. This research intends to apply DOX, which is also an inducer of immunogenic cell death as a part for "in situ vaccination" and conjointly uses PD-1 inhibitors to enhance antitumor efficacy. In order to achieve the sustained vaccination effect and real-time monitoring of distribution in vivo, the in situ forming and injectable hydrogel platform with the function of visualization is established for local delivery. The hydrogel platform is synthesized by hyaluronic acid-dopamine coordinated with gadolinium ions (Gd2+ ). Gd2+ provides the ability of magnetic resonance imaging, meanwhile further cross-linking the hydrogel network. Experiments show excellent ability of sustained release and imaging tracking for the hydrogel platform. In mouse STS models, the "in situ vaccination" hydrogels show the best effect of inhibiting tumor growth. Further analysis of tumor tissues show that "in situ vaccination" group can increase T cell infiltration, promote M1-type macrophage polarization and block elevated PD-1/PD-L1 pathway caused by DOX. These results are expected to prove the potential for synthesized hydrogels to achieve a universal platform for "in situ vaccination" strategies on STS treatments.
Insights
This study developed an injectable hydrogel for soft tissue sarcoma (STS) treatment. The hydrogel delivers doxorubicin (DOX) for in situ vaccination, enhancing immune response and tumor inhibition.
Area of Science:
- Biomaterials Science
- Cancer Immunotherapy
- Drug Delivery Systems
Background:
- Doxorubicin (DOX) is a first-line treatment for soft tissue sarcomas (STS), but its clinical use is limited by dose-dependent toxicity.
- DOX can induce immunogenic cell death, making it a candidate for in situ vaccination strategies.
- Enhancing antitumor efficacy requires strategies to overcome drug toxicity and improve local delivery.
Purpose of the Study:
- To develop an injectable, in situ forming hydrogel platform for sustained local delivery of DOX in STS treatment.
- To utilize the hydrogel for "in situ vaccination" combined with PD-1 inhibitors to boost antitumor immunity.
- To incorporate visualization capabilities for real-time in vivo distribution monitoring.
Main Methods:
- Synthesized a hydrogel platform using hyaluronic acid-dopamine coordinated with gadolinium ions (Gd2+).
- Evaluated the hydrogel's sustained release and in vivo imaging tracking capabilities using magnetic resonance imaging (MRI).
- Tested the efficacy of the "in situ vaccination" hydrogel in mouse STS models, analyzing immune cell infiltration and polarization.
Main Results:
- The developed hydrogel demonstrated excellent sustained release and in vivo imaging tracking.
- Hydrogels used for "in situ vaccination" significantly inhibited tumor growth in mouse STS models.
- Treatment increased T cell infiltration, promoted M1 macrophage polarization, and blocked the PD-1/PD-L1 pathway.
Conclusions:
- The synthesized hydrogel serves as an effective platform for localized DOX delivery and "in situ vaccination" in STS.
- This approach enhances antitumor efficacy by modulating the tumor microenvironment and boosting anti-tumor immunity.
- The hydrogel platform shows potential as a versatile tool for STS treatment strategies.
