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Nanoplateletsomes restrain metastatic tumor formation through decoy and active targeting in a preclinical mouse model
Longlong Zhang1,2, Yuefei Zhu1, Xunbin Wei3
1Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Abstract:
Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.
Insights
Platelet-inspired nanodecoys (nanoplateletsomes) effectively inhibit cancer metastasis by binding circulating tumor cells and preventing their spread. This novel approach shows promise for suppressing lung metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Nanotechnology
Background:
- Platelets play a crucial role in promoting cancer metastasis by aiding cancer cell arrest, adhesion, and extravasation.
- Platelet decoys, devoid of cellular contents, offer a potential strategy to prevent metastatic tumor formation.
Purpose of the Study:
- To develop and evaluate nanoplateletsomes (P-Lipo) for enhanced inhibition of cancer metastasis.
- To investigate the mechanism by which nanoplateletsomes interfere with circulating tumor cells (CTCs) and metastatic processes.
Main Methods:
- Development of nanoplateletsomes by fusing platelet membranes with lipid membranes.
- In vitro assessment of nanoplateletsomes' interaction with CTCs and endothelial cells.
- In vivo evaluation in a mouse breast tumor metastasis model.
Main Results:
- Nanoplateletsomes efficiently bound to CTCs, hindering their arrest by endothelial cells and subsequent extravasation.
- These nanodecoys interfered with tumor cell epithelial-mesenchymal transition.
- In vivo studies demonstrated decreased CTC survival, reduced metastatic tumor growth, and suppressed inflammation.
Conclusions:
- Nanoplateletsomes represent a novel and effective strategy for suppressing cancer metastasis, particularly lung metastasis.
- This approach offers a new therapeutic avenue by leveraging platelet membrane biomimicry to create anti-metastatic nanodecoys.
