Related Experiment Video
Updated: Jul 10, 2025
Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
Published on: April 30, 2021
An injectable, in situ forming and NIR-responsive hydrogel persistently reshaping tumor microenvironment for
Han Zhang1, Liangshan Hu1, Wei Xiao1
1Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
Background:
Melanoma is a highly aggressive form of skin cancer with increasing incidence and mortality rates. Chemotherapy, the primary treatment for melanoma, is limited by hypoxia-induced drug resistance and suppressed immune response at the tumor site. Modulating the tumor microenvironment (TME) to alleviate hypoxia and enhance immune response has shown promise in improving chemotherapy outcomes.
Methods:
In this study, a novel injectable and in situ forming hydrogel named MD@SA was developed using manganese dioxide (MnO2) nanosheets pre-loaded with the chemotherapy drug doxorubicin (DOX) and mixed with sodium alginate (SA). The sustainable drug delivery, oxygen generation ability, and photothermal property of MD@SA hydrogel were characterized. The therapeutic efficacy of hydrogel was studied in B16F10 in vitro and B16F10 tumor-bearing mice in vivo. The immune effects on macrophages were analyzed by flow cytometry, real-time quantitative reverse transcription PCR, and immunofluorescence analyses.
Results:
The MD@SA hydrogel catalyzed the tumoral hydrogen peroxide (H2O2) into oxygen, reducing the hypoxic TME, down-regulating hypoxia-inducible factor-1 alpha (HIF-1α) and drug efflux pump P-glycoprotein (P-gp). The improved TME conditions enhanced the uptake of DOX by melanoma cells, enhancing its efficacy and facilitating the release of tumor antigens. Upon NIR irradiation, the photothermal effect of the hydrogel induced tumor apoptosis to expose more tumor antigens, thus re-educating the M2 type macrophage into the M1 phenotype. Consequently, the MD@SA hydrogel proposes an ability to constantly reverse the hypoxic and immune-inhibited TME, which eventually restrains cancer proliferation.
Conclusion:
The injectable and in situ forming MD@SA hydrogel represents a promising strategy for reshaping the TME in melanoma treatment. By elevating oxygen levels and activating the immune response, this hydrogel offers a synergistic approach for TME regulation nanomedicine.
Insights
This study developed an injectable hydrogel that generates oxygen to combat melanoma's drug resistance and immune suppression. The novel treatment reshapes the tumor microenvironment, enhancing chemotherapy and activating anti-tumor immunity for improved melanoma treatment.
Area of Science:
- Biomaterials Science
- Cancer Nanomedicine
- Immunotherapy
Background:
- Melanoma exhibits increasing incidence and mortality, with chemotherapy efficacy limited by tumor hypoxia and immune suppression.
- Modulating the tumor microenvironment (TME) to alleviate hypoxia and enhance immune response is a promising strategy for improving melanoma treatment outcomes.
Purpose of the Study:
- To develop a novel injectable hydrogel (MD@SA) for melanoma treatment that addresses hypoxia and immune suppression within the TME.
- To investigate the therapeutic efficacy and immune-modulating effects of the MD@SA hydrogel in vitro and in vivo.
Main Methods:
- Developed an injectable, in situ forming hydrogel (MD@SA) using manganese dioxide (MnO2) nanosheets pre-loaded with doxorubicin (DOX) and sodium alginate (SA).
- Characterized the hydrogel's drug delivery, oxygen generation, and photothermal properties.
- Evaluated therapeutic efficacy in B16F10 melanoma cells and tumor-bearing mice, analyzing immune effects on macrophages via flow cytometry, RT-qPCR, and immunofluorescence.
Main Results:
- MD@SA hydrogel converted tumor hydrogen peroxide (H2O2) to oxygen, reducing hypoxia and down-regulating HIF-1α and P-gp, thereby enhancing DOX uptake and efficacy.
- Photothermal effect upon NIR irradiation induced tumor apoptosis, exposing tumor antigens and promoting M2 to M1 macrophage repolarization.
- The hydrogel effectively reversed the hypoxic and immune-inhibited TME, restraining melanoma proliferation.
Conclusions:
- The injectable MD@SA hydrogel is a promising strategy for reshaping the TME in melanoma treatment.
- By increasing oxygen levels and activating immune responses, the hydrogel offers a synergistic approach for TME regulation nanomedicine.
