Photobleaching-mediated charge-convertible cyclodextrin nanoparticles achieve deep tumour penetration for rectal cancer theranostics
Menée à l'aide d'une xénogreffe de cancer rectal sur un modèle murin, cette étude met en évidence l'intérêt théranostique de nanoparticules zwitterioniques capables, en proche infrarouge, de se transformer en particules cationiques et de pénétrer dans la tumeur par transcytose
Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm3) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer.
Nature Nanotechnology , résumé, 2024