Zhang Jingpei, Ma Wei, Yang Boyu, Shi Tingyu, Liao Shenglong, Li Yang, Yin Shouchun
Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education, College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, 311121 Hangzhou, P. R. China.
School of Engineering, Hangzhou Normal University, 311121 Hangzhou, P. R. China.
ACS Appl Mater Interfaces. 2024 Dec 18;16(50):69028-69044. doi: 10.1021/acsami.4c17413. Epub 2024 Dec 4.
The integration of theranostics, which combines diagnostics with therapeutics, has markedly improved the early detection of diseases, precise medication management, and assessment of treatment outcomes. In the realm of oncology, organoplatinum-based supramolecular coordination complexes (SCCs) that can coload therapeutic agents and imaging molecules have emerged as promising candidates for multimodal theranostics of tumors. To address the challenges of tumor-targeted delivery and multimodal theranostics for SCCs, this study employs a cell membrane cloaking strategy to fabricate biomimetic metallacage nanoparticles (MCNPs) with multimodal imaging capabilities and homologous targeting capabilities. Specifically, a photosensitizer molecule (BTTP) containing AIE-active groups was assembled into a metallacage of C-BTTP through Pt-N coordination. This process endows the metallacage with strong NIR-II fluorescence in the aggregated state and significantly superior ROS generation compared to that of the precursor ligand. After being encapsulated with F127, the MCNPs were further cloaked with U87 cancer cell membranes, creating biomimetic MCNPs that achieve tumor-targeting capabilities. Verified by in vitro and in vivo experiments, MCNPs enable multimodal imaging and initiate immunotherapy under photothermal and photodynamic stimulation, leading to synergistic antitumor effects. Furthermore, the evaluation of immunogenic cell death and dendritic cell maturation rate in U87 tumor-bearing mice confirmed the mechanism of photothermal and photodynamic synergistic immunotherapy. This study provides an innovative strategy for enhancing the tumor-targeting and therapeutic efficiency of SCCs, offering a versatile strategy for efficient and minimally invasive theranostics of tumors. The development of such biomimetic nanoparticles represents a significant advancement in the field of nanomedicine, potentially transforming cancer treatment through personalized and targeted therapies.
将诊断与治疗相结合的诊疗一体化显著改善了疾病的早期检测、精准药物管理以及治疗效果评估。在肿瘤学领域，能够共载治疗剂和成像分子的有机铂基超分子配位络合物（SCCs）已成为肿瘤多模态诊疗的有前景的候选物。为应对SCCs的肿瘤靶向递送和多模态诊疗挑战，本研究采用细胞膜包覆策略制备具有多模态成像能力和同源靶向能力的仿生金属笼纳米颗粒（MCNPs）。具体而言，将含有聚集诱导发光（AIE）活性基团的光敏剂分子（BTTP）通过Pt-N配位组装成C-BTTP金属笼。这一过程使金属笼在聚集状态下具有强烈的近红外二区（NIR-II）荧光，并且与前体配体相比，产生活性氧（ROS）的能力显著增强。用F127包裹后，MCNPs进一步用U87癌细胞膜包覆，形成具有肿瘤靶向能力的仿生MCNPs。经体外和体内实验验证，MCNPs能够实现多模态成像，并在光热和光动力刺激下启动免疫治疗，从而产生协同抗肿瘤作用。此外，对荷U87肿瘤小鼠的免疫原性细胞死亡和树突状细胞成熟率的评估证实了光热和光动力协同免疫治疗的机制。本研究为提高SCCs的肿瘤靶向性和治疗效率提供了一种创新策略，为肿瘤的高效微创诊疗提供了一种通用策略。这种仿生纳米颗粒的开发代表了纳米医学领域的一项重大进展，有望通过个性化和靶向治疗改变癌症治疗方式。
