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Published on: July 25, 2022
Lanmodulin-Engineered Outer Membrane Vesicles for Synergistic Targeted Radio-Immunotherapy.
Feifei Zhang1, Zhencun Cui2, Haidong Li1
1MOE Frontiers Science Center for Rare Isotopes and State Key Laboratory of Natural Product Chemistry, Lanzhou University, Lanzhou 730000, China.
ACS Nano
|June 9, 2026
Summary
A novel nanoplatform, TRT@LnOMVs, enhances targeted radionuclide therapy (TRT) and immunotherapy by reprogramming the tumor microenvironment. This radio-immunotherapy approach significantly improves survival rates in prostate cancer models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Targeted radionuclide therapy (TRT) combined with immunotherapy shows promise for cancer treatment.
- Developing adaptable delivery platforms for synergistic radio-immunotherapy is challenging.
- Current methods for radiolabeling face limitations.
Purpose of the Study:
- To develop a programmable, "plug-and-play" nanoplatform for synergistic radio-immunotherapy.
- To enable versatile and efficient radiolabeling of diverse therapeutic radioisotopes.
- To investigate the potential of this platform in overcoming current therapeutic challenges.
Main Methods:
- Engineered outer membrane vesicles (OMVs) from *Salmonella typhimurium* displaying lanmodulin (LanM).
- Facile radiolabeling of diverse isotopes under mild conditions.
- Incorporated lipid-conjugated ligands for precision targeting.
- Utilized single-cell RNA sequencing and transcriptomic analysis to study tumor immune microenvironment remodeling.
Main Results:
- TRT@LnOMVs demonstrated high-efficiency radiolabeling and modular targeting.
- PSMA-targeted TRT@LnOMVs achieved a 90% survival rate in a prostate cancer model, outperforming 177Lu-PSMA-617 (25% survival).
- TRT@LnOMVs significantly remodeled the tumor immune microenvironment by reprogramming myeloid cells, enhancing cytotoxic T and NK cell infiltration, and activating innate immunity.
Conclusions:
- TRT@LnOMVs represent a versatile class of biohybrid therapeutics.
- This platform offers a robust paradigm for next-generation radio-immunotherapy.
- The nanoplatform effectively synergizes targeted radionuclide therapy and immunotherapy for enhanced antitumor responses.
