Hypoxia-Responsive Azobenzene-Linked Hyaluronate Dot Particles for Photodynamic Tumor Therapy

• Main Authors: Sohyeon Lee (Author), Yoonyoung Kim (Author), Eun Seong Lee (Author)
• Format: Book
• Published: MDPI AG, 2022-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14050928; 1999-4923
• Keywords: hypoxia-sensitive; hyaluronate dot particles; ultra-small size; chlorin e6; photodynamic tumor therapy; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 5, p 928 (2022)

In this study, we developed ultra-small hyaluronate dot particles that selectively release phototoxic drugs into a hypoxic tumor microenvironment. Here, the water-soluble hyaluronate dot (dHA) was covalently conjugated with 4,4'-azodianiline (Azo, as a hypoxia-sensitive linker) and Ce6 (as a photodynamic antitumor agent), producing dHA particles with cleavable Azo bond and Ce6 (dHA-Azo-Ce6). Importantly, the inactive Ce6 (self-quenched state) in the dHA-Azo-Ce6 particles was switched to the active Ce6 (dequenched state) via the Azo linker (-N=N-) cleavage in a hypoxic environment. In vitro studies using hypoxia-induced HeLa cells (treated with CoCl₂) revealed that the dHA-Azo-Ce6 particle enhanced photodynamic antitumor inhibition, suggesting its potential as an antitumor drug candidate in response to tumor hypoxia.