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

Abstract

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.