重组溶瘤腺病毒提供了一种新颖且有前途的癌症治疗方法，但其单独疗效仍然有限。本研究探讨了一种联合治疗策略，通过将载有重组溶瘤 Adv 的丝水凝胶与 PD-L1 抑制剂联合给药来治疗膀胱癌患者，以提高治疗效果。收集小鼠膀胱癌组织并进行单细胞测序，确定CRB3是恶性细胞中的关键基因。进行差异表达和功能富集分析，通过体外实验验证 CRB3 的抑制作用，显示抑制膀胱癌细胞增殖、迁移和侵袭。构建编码CRB3和GM-CSF的重组溶瘤腺病毒并将其封装在丝水凝胶中以提高药物负载和释放效率。体内实验表明，纳米复合水凝胶显着抑制肿瘤生长并增加肿瘤组织中的免疫浸润。腺病毒丝水凝胶 (Adv-CRB3@gel) 与 PD-L1 抑制剂的共同给药显着增强了 T 细胞浸润和肿瘤杀伤。编码 CRB3 和 GM-CSF 的重组溶瘤 Adv 纳米复合水凝胶与 PD-L1 抑制剂的组合通过有效招募 T 细胞改善膀胱癌治疗结果，提供一种新颖的治疗策略。© 2024。作者。

Recombinant oncolytic adenovirus offers a novel and promising cancer treatment approach, but its standalone efficacy remains limited. This study investigates a combination treatment strategy by co-administering recombinant oncolytic Adv-loaded silk hydrogel with a PD-L1 inhibitor for patients with bladder cancer to enhance treatment outcomes. Bladder cancer tissues from mice were collected and subjected to single-cell sequencing, identifying CRB3 as a key gene in malignant cells. Differential expression and functional enrichment analyses were performed, validating CRB3's inhibitory role through in vitro experiments showing suppression of bladder cancer cell proliferation, migration, and invasion. Recombinant oncolytic adenoviruses encoding CRB3 and GM-CSF were constructed and encapsulated in silk hydrogel to enhance drug loading and release efficiency. In vivo experiments demonstrated that the nano-composite hydrogel significantly inhibited tumor growth and increased immune infiltration in tumor tissues. Co-administration of adenovirus silk hydrogel (Adv-CRB3@gel) with a PD-L1 inhibitor significantly enhanced T-cell infiltration and tumor killing. The combination of recombinant oncolytic Adv-loaded nano-composite hydrogel encoding CRB3 and GM-CSF with a PD-L1 inhibitor improves bladder cancer treatment outcomes by effectively recruiting T cells, providing a novel therapeutic strategy.© 2024. The Author(s).