Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
J Control Release. 2022 Oct;350:215-227. doi: 10.1016/j.jconrel.2022.08.025. Epub 2022 Aug 22.
Intelligent nanomedicines integrated with stimuli-responsive components enable on-demand customizable treatment options which would improve therapeutic outcome and reduce systemic toxicity. In this work, we explore the synergistic therapeutic potential of photodynamic therapy and immunometabolic modulation to achieve tumour regression and to trigger an adaptive immunity to prevent tumour recurrence. The therapeutic potential of the fabricated Bioengineered Immunomodulatory Organelle targeted Nanozymes (BIONs) was tested on 3D printed mini-brains which could effectively recapitulate the biologically relevant interactions between glioblastoma cells and macrophages. In the presence of glioblastoma organotypic brain slices, activated BIONs upregulated the cell surface expression of CD86, a costimulatory molecule and CD83, maturation marker, on monocyte derived dendritic cells, suggesting its ability to elicit a strong immune response. Furthermore, the antigen pulsed dendritic cells by chemotaxis and transendothelial migration readily relocate into the draining lymph node where they present the antigenic cargo to enable the proliferation of T lymphocytes. The stealth and tunable catalytic activity of BIONs prevent ROS mediated diseases such as acute kidney injury by providing environment dependent protection without compromising on its promising anti-cancer activity.
智能纳米药物与刺激响应组件集成，可实现按需定制的治疗选择，从而改善治疗效果并降低全身毒性。在这项工作中，我们探索了光动力疗法和免疫代谢调节的协同治疗潜力，以实现肿瘤消退并触发适应性免疫以防止肿瘤复发。所制备的靶向生物工程免疫调节细胞器的纳米酶（BIONs）的治疗潜力在 3D 打印的迷你大脑上进行了测试，该迷你大脑可以有效地再现脑胶质瘤细胞和巨噬细胞之间具有生物学相关性的相互作用。在脑胶质瘤器官型脑切片存在的情况下，激活的 BIONs 上调了单核细胞衍生树突状细胞表面的共刺激分子 CD86 和成熟标志物 CD83 的表达，表明其能够引发强烈的免疫反应。此外，趋化作用和跨内皮迁移的抗原脉冲树突状细胞可轻易转移到引流淋巴结，在那里它们将抗原性货物呈递给 T 淋巴细胞，以促进 T 淋巴细胞的增殖。BIONs 的隐身性和可调催化活性通过提供依赖于环境的保护来预防 ROS 介导的疾病（如急性肾损伤），而不会影响其有前途的抗癌活性。
