Sialic Acids Blockade-Based Chemo-Immunotherapy Featuring Cancer Cell Chemosensitivity and Antitumor Immune Response
Xiang Zhang1, Zi-Yi Li1, Jia-Heng Xiao1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, and Chemical Biology Center, Peking University, Beijing, 100191, China.
Advanced Healthcare Materials
|June 28, 2024
Summary
This study introduces novel nanoparticles (NCP-STI) that block cancer
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Immune checkpoint blockade (ICB) shows limited efficacy in many cancer patients.
- Cancer cells often overexpress sialic acid glycans, promoting immune evasion and disease progression.
- Targeting the sialic acid glyco-immune checkpoint offers a new therapeutic avenue.
Purpose of the Study:
- To develop novel nanoparticles (NCP-STI) for disrupting the sialic acid glyco-immune checkpoint.
- To investigate NCP-STI's ability to inhibit cancer cell sialylation and enhance chemotherapy.
- To evaluate the combined chemo-immunotherapy efficacy of NCP-STI and gemcitabine (Gem).
Main Methods:
- Self-assembled core-shell nanoscale coordination polymer nanoparticles (NCPs) loaded with a sialyltransferase inhibitor (STI).
- Administration of NCP-STI to cancer cells to strip sialoglycans and inhibit sialylation of CNT1.
- Combination therapy using NCP-STI and gemcitabine (Gem) in murine tumor models.
Main Results:
- NCP-STI effectively removed sialoglycans from cancer cells, disrupting the Siglec-sialic acid checkpoint independently of antibodies.
- NCP-STI enhanced intracellular accumulation of gemcitabine and promoted gemcitabine-induced immunogenic cell death (ICD).
- The combination of NCP-STI and Gem demonstrated significant antitumor efficacy against various murine tumors and pulmonary metastasis.
Conclusions:
- NCP-STI represents a novel small molecule-based approach to chemo-immunotherapy.
- Sialic acid blockade by NCP-STI synergistically enhances chemotherapy sensitivity and antitumor immune responses.
- This strategy offers a promising new avenue for cancer treatment by combining chemical and immune therapies.
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