Platelet-Membrane-Coated Nanoparticles Enable Vascular Disrupting Agent Combining Anti-Angiogenic Drug for Improved Tumor Vessel Impairment

Abstract

Compared with traditional chemotherapeutics, vascular disruption agents (VDAs) have the advantages of rapidly blocking the supply of nutrients and starving tumors to death. Although the VDAs are effective under certain scenarios, this treatment triggers angiogenesis in the later stage of therapy that frequently leads to tumor recurrence and treatment failure. Additionally, the nonspecific tumor targeting and considerable side effects also impede the clinical applications of VDAs. Here we develop a customized strategy that combines a VDA with an anti-angiogenic drug (AAD) using mesoporous silica nanoparticles (MSNs) coated with platelet membrane for the self-assembled tumor targeting accumulation. The tailor-made nanoparticles accumulate in tumor tissues through the targeted adhesion of platelet membrane surface to damaged vessel sites, resulting in significant vascular disruption and efficient anti-angiogenesis in animal models. This study demonstrates the promising potential of combining VDA and AAD in a single nanoplatform for tumor eradication.

Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications

“…Similar to the RBCs and WBCs, platelets are essential components in mammalian blood cells and understandably have attracted remarkable attention from researchers for the fabrication of membrane-coated NPs; this is because of their hemostasis and immune response properties [23]. Based on these favorable properties, NPs coated with the membrane components of platelets have been successfully used [2,3] for site-specific delivery, cancer therapy, and enhanced magnetic resonance imaging.…”

Bacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy

“…[13,14] The destroying or obstructing established blood vessels strategy is employed using vascular disrupting or embolic agents. [15,16] Notably, vascular occlusion can deprive tumors of oxygen and nutrients within hours after thrombosis and decrease the risk of resistance development. [17] As blood vessels of solid tumors are essentially similar, thrombosis-based vessel targeting therapy can be widely applied to target many types of tumors.…”

“…[ 10 ] Therefore, attention has focused on targeting tumor blood vessels to suspend tumor progression by disrupting the function of the vasculature. [ 11 , 12 ] Based on the different mechanisms involved, two vessel targeting therapies are prevalent, that is, antiangiogenesis and destroying or obstructing the established blood vessels. For antiangiogenesis, the angiogenesis pathways are disrupted by vascular endothelial growth factor antibodies or using copper ion inhibitors to prevent the formation of new blood vessels.…”

Regulating Acidosis and Relieving Hypoxia by Platelet Membrane-Coated Nanoparticle for Enhancing Tumor Chemotherapy

“…Although ZIF8 NPs could passively target tumor tissue through the enhanced permeability and retention (EPR) effect, it still suffered lower targeting efficiency and certain biological toxicity. With respect to this, we coated platelet membrane (PM) on the surface of the composite NPs, which would not only endow the NPs active targeting ability to the tumor but also improve their biocompatibility ( Hu et al, 2015 ; Liu G. et al, 2019 ; Zhang et al, 2019 ; Li et al, 2021 ). There is no doubt that the synergy of active targeting and the EPR effect will significantly increase the accumulation efficiency of NPs in tumor tissue.…”