Tumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci. Here we engineered a peptide-based surface-fill hydrogel (SFH) that can be syringe- or spray-delivered to surface cancers during surgery or used as a primary therapy. Once applied, SFH can shape change in response to alterations in tissue morphology that may occur during surgery. Implanted SFH releases nanoparticles composed of microRNA and intrinsically disordered peptides that enter cancer cells attenuating their oncogenic signature. With a single application, SFH shows efficacy in four preclinical models of mesothelioma, demonstrating the therapeutic impact of the local application of tumour-specific microRNA, which might change the treatment paradigm for mesothelioma and possibly other surface cancers.

在拓扑结构复杂的器官和组织表面以片状方式生长的肿瘤是一种难以治疗的临床情况。由于病变组织的解剖结构复杂，因此很难通过手术完全切除。残留癌通常对全身治疗反应不佳，局部治疗因显微镜下肿瘤病灶的可及性有限而受阻。在这里，我们设计了一种基于肽的表面填充水凝胶 (SFH)，可以在手术期间通过注射器或喷雾器将其输送到表面癌症或用作主要疗法。一旦应用，SFH 可以响应手术过程中可能发生的组织形态学变化而改变形状。植入的 SFH 释放出由 microRNA 和本质上无序的肽组成的纳米颗粒，这些纳米颗粒进入癌细胞，减弱了它们的致癌特征。