In situ hydrogelation of forky peptides at prostate tissue for drug delivery

Herein, we have designed and synthesized a novel forky peptide D3F3 that would transform into hydrogels through crosslinking induced by ZIs stimuli. We have employed D3F3 as the suitable carrier for its conjugation with DOX. Since the triggering concentration of zinc ions falls into the physiologic range at prostate tissue and other cationic ions fail to do the triggering at the physiologic concentrations, the peptide-based drug delivery system (DDS) are injectable and would achieve prostate tissue-specific self-assembly in situ. The D3F3 hydrogels exhibit an optimal gelation time, satisfactory mechanical strength(can be enhanced after incorporating of DOX) as well as excellent thixotropic properties. The DDS realized some DOX even reserved in prostate 24h after the injection, it make local sustained release possible. In addition, the peptide materials demonstrated no cytotoxicity against normal fibroblast cell and no damage to prostate tissue of rat. The drug release followed a non-Fickian diffusion model, with no burst release observed. Importantly, the DOX-hydrogel system exhibited well anti-cancer efficacy when incubated with prostate cancer cells DU-145. Therefore, this work lays the groundwork for future design of tissue-specific DDS that are triggered by cationic ions (e.g. Zinc ions), and the platform could be further developed to incorporate other potent drugs utilized in the field of prostate cancer therapy, thereby increasing the potency and reducing their side effects.