Sodium hyaluronate-tetrazine biopolymer (SQL70) (SQL70)

SQL70 is a synthetic biopolymer consisting of a sodium hyaluronate backbone covalently modified with tetrazine functional groups, developed by Shasqi as a core component of the Click Activated Protodrugs Against Cancer (CAPAC) platform (Shasqi, 2024). It is designed to be administered via intratumoral injection, where its high molecular weight and gel-like properties allow it to remain localized within the tumor microenvironment for several weeks. Once in place, SQL70 serves as a chemical "docking station" or target for systemically administered protodrugs that have been modified with a trans-cyclooctene (TCO) moiety, such as SQP33 (Mejia Oneto et al., 2016, ACS Central Science). The tetrazine groups on the biopolymer react specifically and rapidly with the TCO groups on the protodrug via an inverse electron-demand Diels-Alder (IEDDA) reaction, leading to the cleavage of the linker and the release of the active cytotoxic payload directly at the tumor site. This approach allows for the delivery of significantly higher doses of chemotherapy to the tumor while minimizing systemic exposure and associated toxicities. SQL70 is currently being evaluated in clinical trials as part of the SQ3370 therapeutic regimen for the treatment of advanced solid tumors (ClinicalTrials.gov, NCT04106492).

Other names

Tetrazine-modified hyaluronic acidSQL70 biopolymerTetrazine-functionalized sodium hyaluronateCAPAC biopolymer

SQL70 functions as a localized chemical activator that captures systemically administered trans-cyclooctene (TCO)-modified protodrugs through a rapid, bioorthogonal inverse electron-demand Diels-Alder (IEDDA) reaction, which triggers the site-specific release of the active therapeutic agent (Wu et al., 2021, Journal for ImmunoTherapy of Cancer).