Interventional Cancer Institute of Chinese Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
J Nanobiotechnology. 2024 Oct 16;22(1):630. doi: 10.1186/s12951-024-02909-3.
Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA) in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous HO. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8 T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.
光热疗法(PTT)是一种很有前途的非侵入性治疗方法,在消除肿瘤方面显示出巨大的潜力。它不仅诱导癌细胞凋亡,还触发免疫原性细胞死亡(ICD),从而激活免疫系统对抗癌症。然而,免疫抑制性肿瘤微环境(TIME)对单一治疗引发强烈免疫反应构成挑战,从而限制了癌症免疫治疗的疗效。在这项研究中,双靶向纳米递药系统(GOx@FeNPs)联合αPD-L1 免疫检查点抑制剂可以通过介导 PTT、铁死亡和抗肿瘤免疫反应来抑制结直肠癌(CRC)的进展。简而言之,GOx@FeNPs 中的环状精氨酸-甘氨酸-天冬氨酸(cRGD)肽和茴香酰胺(AA)实现了特异性肿瘤递药,不仅具有良好的光热效应,实现 PTT 和诱导 ICD,还可以耗竭谷胱甘肽(GSH)并催化内源性 HO 产生活性氧(ROS)。所有这些都加速了芬顿反应,增强了 PTT 诱导 ICD 的过程。因此,大量肿瘤特异性抗原被释放出来,刺激淋巴结中树突状细胞(DCs)的成熟,并增强 CD8 T 细胞在肿瘤中的浸润。同时,与αPD-L1 联合使用对 CRC 具有良好的协同疗效,肿瘤抑制率超过 90%。此外,由于 Fe 的存在,GOx@FeNPs 在 T2 加权磁共振成像(MRI)下具有良好的磁共振成像(MRI)能力,有利于 CRC 的综合诊断和治疗系统。通过构建双靶向 GOx@FeNPs 纳米平台,实现了 PTT 与铁死亡的协同作用,提高了免疫治疗效果,为 CRC 免疫治疗提供了新的途径。
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