Abstract：
Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.
摘要：
直接向肿瘤微环境(TME)供应抗癌药物的药物局部递送系统导致优异的肿瘤控制并使与抗癌药物相关的副作用最小化。免疫检查点抑制剂（ICIs）一直是癌症免疫治疗的支柱。然而,ICIs的全身给药伴随着相当大的免疫治疗相关毒性.探讨通过缓释凝胶形成载体局部施用的抗PD-L1抗体是否保留其有效的抗癌功能，同时引起较少的结肠炎样副作用，CT,以前报道的仓库系统，用于将抗PD-L1抗体与姜黄素一起局部递送至患有膀胱癌的溃疡性结肠炎模型小鼠中的TME。我们表明，CT介导的抗PD-L1抗体和姜黄素的肿瘤内共注射能够持续释放负载的抗PD-L1抗体和姜黄素，这有助于对UC模型小鼠的结肠具有可忽略的副作用的实质性抗癌作用。然而,尽管抗PD-L1抗体与CT介导的姜黄素的肿瘤内递送在抑制肿瘤生长方面具有系统性协同作用，通过腹膜内施用抗PD-L1抗体，结肠炎显著恶化。这些发现表明，CT是抗癌药物局部递送的有前途的药物，因为它可以保留有效的抗癌功能，同时大大减少与这些药物的全身给药相关的不良副作用。
