Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun 130022, PR China.
Key Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
Biomater Sci. 2022 Sep 27;10(19):5596-5607. doi: 10.1039/d2bm00988a.
Tumor stroma plays an important role in the occurrence, development, and metastasis of colorectal cancer (CRC). The dense collagenous stroma forms a physical barrier for antitumor drugs and sustains a highly tumor immunosuppressive microenvironment. To address this issue, a spatiotemporal combination of antitumor stroma and nanoscale functional materials was used as an antitumor strategy for reprogramming the tumor immune microenvironment. In this combination, metformin hydrochloride (MET) was intraperitoneally injected to disrupt the dense tumor stroma for promoting drug delivery and remodeling the tumor immune microenvironment. Subsequently, intravenously injected multifunctional drug-delivery materials (MIL-100/mitoxantrone/hyaluronic acid nanoparticles, MMH NPs) were visualized by double imaging (photoacoustic (PA) and fluorescence imaging) and generated a robust immune response immunogenic cell death (ICD). More importantly, the combination treatment also acted synergistically with the anti-OX40 agonist antibody (αOX40), which enhanced the treatment of orthotopic CRC. In summary, the combination strategy of MET/MMH NPs/αOX40 provides a novel and effective clinical option for CRC therapy.
肿瘤基质在结直肠癌（CRC）的发生、发展和转移中起着重要作用。密集的胶原基质为抗肿瘤药物形成物理屏障，并维持高度肿瘤免疫抑制的微环境。为了解决这个问题，将抗肿瘤基质和纳米级功能材料的时空组合用作重编程肿瘤免疫微环境的抗肿瘤策略。在这种组合中，盐酸二甲双胍（MET）被腹腔注射以破坏密集的肿瘤基质，以促进药物传递和重塑肿瘤免疫微环境。随后，通过双成像（光声（PA）和荧光成像）可视化静脉注射的多功能药物递送材料（MIL-100/米托蒽醌/透明质酸纳米颗粒，MMH NPs），并产生强大的免疫反应——免疫原性细胞死亡（ICD）。更重要的是，联合治疗还与抗 OX40 激动剂抗体（αOX40）协同作用，增强了对原位 CRC 的治疗效果。总之，MET/MMH NPs/αOX40 的联合治疗策略为 CRC 治疗提供了一种新颖有效的临床选择。
