Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Jilin University, Changchun 130031, PR China.
Department of Biochemistry, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, PR China.
Acta Biomater. 2022 May;144:132-141. doi: 10.1016/j.actbio.2022.03.023. Epub 2022 Mar 18.
Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.
由于肿瘤的分子异质性，肿瘤治疗的临床效果并不十分令人满意，因此需要新的策略来应对这一挑战。联合治疗可以通过刺激多种途径，降低单药治疗的全身毒性，调节肿瘤免疫微环境，有效地增强肿瘤治疗效果。在此，通过微波辅助法合成了金属有机骨架 MIL-100(Fe)纳米粒子（NPs），然后将奥沙利铂（OXA）和吲哚菁绿（ICG）载入透明质酸（HA）修饰的 MIL-100 NPs 中，得到多功能纳米粒子（OIMH NPs）。OIMH NPs 具有灵敏的光声成像（PAI），可用于成像引导治疗，并通过化疗与光热治疗（PTT）相结合杀死肿瘤细胞，表现出良好的协同效应。化疗-光热治疗诱导的免疫原性细胞死亡（ICD）和 T 细胞激活可以增强免疫检查点阻断（aPD-L1）的反应，从而引发全身抗肿瘤免疫。最后，观察到肿瘤抑制作用，这归因于化疗、PTT 和 aPD-L1 的联合作用。基于研究结果，提出了一种创新的基于多功能 NPs 的成像介导联合治疗策略，这可能为结直肠癌的临床治疗提供新的方法。
