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Biomimetic mineralized DCPA/ anti-CD47 containing thermo-sensitive injectable hydrogel for bone-metastatic prostate
Shenglong Tan1, Qianqian Wang2, Chunxiang Feng2
1Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, China.
Abstract:
Strategies that leverage the phagocytic capabilities of M1 macrophages against tumor cells are currently being investigated for cancer treatment. However, the clinical application of these strategies is significantly hampered by the severe side effects associated with conventional M1 macrophage activators. In this study, biomimetic mineralized dicalcium phosphate anhydrous (MDCPA) was synthesized using Zein as an organic template, aiming to promote M1 macrophage polarization effectively while minimizing side effects. In vitro experiments demonstrated that MDCPA can be engulfed by macrophages and induce M1 macrophage polarization. By combining the stimulation of MDCPA with a commonly used immune checkpoint inhibitor, anti-CD47 (aCD47), the macrophages exhibited the highest phagocytic activity toward prostate cancer cells. Further in vivo experiments illustrated significant tumor suppression and reduced bone resorption in a prostate cancer bone metastasis model utilizing MDCPA/aCD47-containing thermos-sensitive injectable hydrogels (MDCPA/aCD47 TSI gel). Mechanistic studies indicated that the MDCPA/aCD47 TSI gel promotes tumor cell apoptosis not only through the phagocytosis of tumor cells mediated by M1 macrophages, but also by activating anti-tumor CD8-positive T cells. Consequently, this composite gel platform presents an effective theragnostic strategy for treating prostate cancer bone metastasis without the associated side effects, facilitated by biomimetic minerals that mediate anti-tumor immunity.
Insights
Biomimetic minerals (MDCPA) activate M1 macrophages to target cancer cells. Combined with anti-CD47, this approach suppresses prostate cancer bone metastasis with minimal side effects, activating anti-tumor T cells.
Area of Science:
- Biomaterials Science
- Immunology
- Oncology
Background:
- M1 macrophages show promise in cancer therapy by phagocytosing tumor cells.
- Conventional activators cause severe side effects, limiting clinical use.
- Developing safe and effective M1 macrophage activators is crucial for cancer treatment.
Purpose of the Study:
- To synthesize biomimetic mineralized dicalcium phosphate anhydrous (MDCPA) for M1 macrophage activation.
- To evaluate MDCPA's efficacy in promoting M1 polarization and macrophage phagocytosis.
- To develop a composite hydrogel platform for treating prostate cancer bone metastasis with reduced side effects.
Main Methods:
- Synthesized MDCPA using Zein as an organic template.
- Performed in vitro studies to assess macrophage polarization and phagocytosis.
- Combined MDCPA with anti-CD47 (aCD47) and formulated into thermos-sensitive injectable hydrogels (MDCPA/aCD47 TSI gel).
- Evaluated tumor suppression and bone resorption in a prostate cancer bone metastasis model.
Main Results:
- MDCPA successfully induced M1 macrophage polarization and phagocytosis in vitro.
- MDCPA/aCD47 combination significantly enhanced macrophage phagocytic activity against prostate cancer cells.
- MDCPA/aCD47 TSI gel demonstrated significant tumor suppression and reduced bone resorption in vivo.
- The gel activated anti-tumor CD8-positive T cells, contributing to tumor cell apoptosis.
Conclusions:
- MDCPA is a safe and effective biomaterial for M1 macrophage activation.
- The MDCPA/aCD47 TSI gel platform offers a promising theranostic strategy for prostate cancer bone metastasis.
- This approach leverages biomimetic minerals to mediate anti-tumor immunity with minimal side effects.
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