Tumor Microenvironment Triggered In Situ Coagulation of Supramolecularly Engineered Platelets for Precise Tumor Embolization.

Abstract

Although embolization therapy has demonstrated success in impeding tumor growth, concerns persist regarding potential tumor recurrence and inadvertent embolization of non-target tissues. In this study, drawing inspiration from the natural targeting and coagulation process of platelets in injured blood vessels, platelets are engineered by integrating acid-sensitive, morphology-transformable nanoparticles onto their surface through supramolecular conjugation (PLT-NP). The nanoparticles are constructed through the self-assembly of a β-amyloid derived peptide (FFVLK) terminally functionalized with Fmoc, hexahistidine (His₆), and a polyethylene glycol (PEG)-functionalized cyclodextrin (CD). The supramolecularly engineered platelets actively accumulate in the tumor tissue upon inducing a tumor blood vessel injury through tumor resection. In response to the local acidic microenvironment, the nanoparticles undergo a morphological transformation into nanofibers via spontaneous assembly of FFLVK into fibril structures through hydrogen bonding and β-sheet interactions, to artificially enhance the coagulation and aggregation of platelets, causing occlusion of tumor blood vessels. The supramolecularly engineered platelets efficiently embolize tumor blood vessels in a specific manner, effectively suppressing tumor growth, metastasis, and recurrence, thus offering a promising paradigm for combating cancer.