Injectable catechin-based supramolecular hydrogel for highly efficient application in HPV-associated OSCC

Catechins are a group of natural polyphenols extracted from green tea. Notably, they have been proven to have excellent anti-HPV and anti-tumour properties and to be effective against some HPV-related diseases, showing great potential in the treatment of HPV-associated oral squamous cell carcinoma (HPV⁺ OSCC). However, the poor bioavailability, short half-lives, and stability issues of catechins hamper their clinical application. To overcome these shortcomings of catechins, we innovatively synthesised an injectable supramolecular hydrogel, namely catechin-phenylenebisboronic acid-isoguanosine (CPBisoG), with catechin (one of the simplest catechins) and isoguanosine (isoG), another natural product with self-assembly ability, via dynamic phenylborate diester bonds. The biodegradation and sustained-release time of the CPBisoG hydrogel in mice lasted up to 72 h. This supramolecular hydrogel not only functioned as a good local drug delivery platform with good stability, injectability, self-healing properties, biocompatibility, biodegradability, but also exhibited therapeutic effects toward HPV⁺ OSCC in vitro and in vivo. And interestingly, it also showed selective inhibition against HPV⁺ OSCC cells. In all, these results demonstrate that this catechin-based hydrogel could sustainedly and highly effectively treat HPV⁺ OSCC topically, which could also provide a promising strategy for the management of other HPV-associated diseases in the future.