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Neutrophil-Mediated Tumor Discrimination Biomimetic Nanodevice for Precise Tumor Eradication and Metastasis Cascade
Nan Wang1,2,3, Mingjian Zhu1, Yiming Jiang1
1State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Abstract:
The deficient discrimination of tumor cells, limited accumulation of therapeutic agents in tumor foci, and undesirable tumor metastasis result in compromised therapeutic efficacy in antitumor therapy. Neutrophils, the most abundant circulating leukocytes, are key players in tumor progression and have a high affinity to tumors. Herein, a biomimetic tumor discrimination nanodevice (NL-FSB) is developed by harboring a pH-sensitive Fenton agent (FSB) in an activated neutrophil membrane-incorporated liposome for tumor-specific ablation. Inheriting the biointerfacing properties of neutrophils, NL-FSB is endowed with high affinity to tumors. On one hand, NL-FSB can be recruited to acidic tumor sites mediated by chemotaxis attraction and selectively generate reactive oxygen species via amplified Fenton chemical reaction for specific tumor eradication. On the other hand, the biomimetic NL-FSB can also target and bind tumor vascular endothelium or circulating tumor cells (CTCs) in circulation, executing pseudo escort to perturb CTC-neutrophil cluster formation and tumor metastasis cascade. Unprecedentedly, the neutrophil-mediated nanoagent can effectively inhibit the already-formed tumor and prevent tumor metastasis with high specificity. Our study represents a promising yet simple strategy for tumor-specific killing and metastasis cascade blockage via a nanobioengineering functionalization strategy.
Insights
This study introduces a neutrophil-inspired nanodevice that targets tumors, eradicating them via reactive oxygen species and preventing metastasis. This biomimetic approach enhances antitumor therapy and blocks cancer spread.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Antitumor therapy faces challenges like poor tumor cell discrimination, limited drug accumulation, and metastasis.
- Neutrophils, abundant leukocytes, promote tumor progression and exhibit high tumor affinity.
Purpose of the Study:
- To develop a biomimetic nanodevice for tumor-specific ablation and metastasis inhibition.
- To leverage neutrophil properties for enhanced cancer treatment efficacy.
Main Methods:
- Fabrication of a nanodevice (NL-FSB) by encapsulating a pH-sensitive Fenton agent (FSB) within a neutrophil membrane-coated liposome.
- Utilizing the nanodevice's neutrophil-like properties for tumor targeting and reactive oxygen species generation.
- Investigating the nanodevice's ability to inhibit primary tumors and prevent metastasis of circulating tumor cells (CTCs).
Main Results:
- The NL-FSB nanodevice demonstrated high affinity for tumors, accumulating at acidic tumor sites.
- Acidic conditions amplified Fenton reactions, leading to specific tumor eradication via reactive oxygen species.
- The nanodevice effectively inhibited primary tumors and prevented metastasis by interfering with CTC-neutrophil interactions.
Conclusions:
- Neutrophil-inspired nanodevices offer a promising strategy for tumor-specific killing.
- This approach effectively blocks the tumor metastasis cascade.
- Nanobioengineering functionalization provides a simple yet potent strategy for advanced cancer therapy.
