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Soft cell-derived hybrid microparticles with platelet decoys for enhanced cancer chemotherapy
Nana Bie1, Shiyu Li1, Kaili Sun1
1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Abstract:
Platelets play a critical role in tumor development, metastasis and chemoresistance, making the effective killing of tumor cells and simultaneously targeted disruption of platelet functions essential for improving cancer treatment outcomes, especially in post-surgical malignant tumor patients. Here, we develop soft hybrid microparticles (3D-PMPs) by fusing tumor-repopulating cell-derived microparticles with inactivated platelet membranes to deliver the anticancer agent doxorubicin (DOX@3D-PMPs). Leveraging their unique softness, DOX@3D-PMPs demonstrate superior tumor accumulation, deep tumor penetration, and enhanced internalization into tumor cells, leading to efficient tumor cell killing. Additionally, 3D-PMPs function as highly targeted platelet decoys to disrupt platelet-tumor cell interaction and reduce platelet-driven tumor proliferation and metastasis. Mechanistically, Toll-like receptor 4 (TLR-4) presented on 3D-PMPs is responsible for their platelet decoy function. DOX@3D-PMPs demonstrate significantly enhanced therapeutic efficacy in both orthotopic 4T1 breast tumors and post-surgical orthotopic 4T1 breast tumors. This work offers a novel and effective approach to enhance the therapeutic outcomes in cancer treatment, particularly in post-surgical settings.
Insights
New hybrid microparticles deliver chemotherapy and disrupt platelet interactions, improving cancer treatment. These soft particles target tumors effectively, reducing metastasis and enhancing outcomes, especially after surgery.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Platelets significantly influence tumor progression, metastasis, and chemoresistance.
- Targeting platelet functions alongside tumor cell killing is crucial for effective cancer therapy, particularly in post-surgical patients.
Purpose of the Study:
- To develop novel soft hybrid microparticles (3D-PMPs) for targeted cancer therapy.
- To investigate the dual function of these microparticles in delivering chemotherapy and disrupting platelet-tumor cell interactions.
Main Methods:
- Fabrication of soft hybrid microparticles (3D-PMPs) by fusing tumor cell-derived microparticles with inactivated platelet membranes.
- Encapsulation of doxorubicin (DOX) into 3D-PMPs (DOX@3D-PMPs) for drug delivery.
- Evaluation of DOX@3D-PMPs' tumor accumulation, penetration, internalization, and therapeutic efficacy in orthotopic 4T1 breast tumor models, including post-surgical settings.
- Investigation of the mechanism underlying the platelet decoy function, focusing on Toll-like receptor 4 (TLR-4).
Main Results:
- DOX@3D-PMPs exhibited enhanced tumor accumulation, deep penetration, and cellular internalization.
- The microparticles demonstrated efficient tumor cell killing and significantly reduced platelet-driven tumor proliferation and metastasis.
- The platelet decoy function was mechanistically linked to Toll-like receptor 4 (TLR-4) expression on the microparticles.
- Significantly improved therapeutic efficacy was observed in both orthotopic and post-surgical breast tumor models.
Conclusions:
- Soft hybrid microparticles (DOX@3D-PMPs) offer a promising strategy for combined chemotherapy delivery and platelet function disruption.
- These microparticles show superior tumor targeting and penetration, leading to enhanced anti-cancer effects.
- The findings highlight a novel approach to improve cancer treatment outcomes, especially in challenging post-surgical scenarios.
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