Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.
Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Int J Oral Sci. 2023 Feb 10;15(1):9. doi: 10.1038/s41368-022-00211-2.
Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
癌细胞膜（CCM）衍生的纳米技术使纳米粒子（NPs）具有识别同源细胞的功能，在精确肿瘤治疗中具有转化潜力。然而，这些纳米平台主要由固定细胞系产生，通常在细胞系衍生的皮下异种移植（CDX）中进行评估，忽略了肿瘤异质性和个体间以及异位和原位肿瘤之间的微环境的分化，限制了这些纳米平台的治疗效率。在此，通过在 Au@C NP 表面涂覆头颈部鳞状细胞癌（HNSCC）细胞系和患者来源细胞的 CCM，制备了各种仿生纳米平台（CCM 修饰的金@碳，即 Au@C-CCM）。生成的 Au@C-CCM 在相应的 CDX、舌原位异种移植（TOX）、免疫功能正常的原发性和远处肿瘤模型以及患者来源的异种移植（PDX）模型上进行了评估。Au@C-CCM 为原发性 HNSCC 治疗产生高达 44.2%的光热转换效率，并通过光热治疗诱导的免疫原性细胞死亡引发免疫治疗来抑制转移。同源 CCM 赋予纳米平台最佳的靶向特性，以实现最高的治疗效率，远远超过那些具有不匹配 CCM 的纳米平台，从而在所有四个模型中实现了明显的肿瘤消融和肿瘤生长抑制。这项工作加强了仿生 NPs 结合模块化设计的 CMs 和功能核心用于 HNSCC 定制治疗的可行性，可进一步扩展到其他恶性肿瘤治疗。
