Target-anchoring nanofibers with retention-enhanced drug delivery for synergistic chemo-photothermal therapy of ovarian cancer.

In patients with advanced ovarian cancer, a formidable "drug barrier" formed by interstitial pressure and postsurgical adhesions severely limits the tumor accumulation of intravenously administered chemotherapeutics, leading to sub-therapeutic tumor exposure and inevitable chemoresistance. Injectable short-fiber systems represent a promising localized platform to circumvent the drug barrier; however, their application is limited by poor intratumoral retention of the nanofibers, passive drug release, and a lack of targeting affinity. Here, we present an injectable target-anchoring short nanofiber (TASF) system designed to overcome these multifactorial barriers. TASF integrates a 3D interlocking network for mechanical anchoring, a polydopamine coating for chemical adhesion, folate ligands for tumor-targeted affinity, and an NIR-responsive component for controlled activation. After intratumoral administration, TASF remains stably anchored and is activated by NIR irradiation, triggering rapid drug release and localized photothermal therapy. This design ensures potent chemo-photothermal action is confined to tumor tissues. In ovarian cancer models, NIR-activated TASF treatment downregulates resistance-related protein expression and leads to robust tumor growth suppression. Importantly, the synergistic action of robust adhesion, targeting affinity, and NIR-controlled activation minimizes off-target effects, thereby enhancing the safety profile. This work provides a promising local delivery strategy to circumvent interstitial pressure and stromal barriers that limit drug penetration in solid tumor therapy, offering potential insights for future localized treatment of ovarian cancer.