Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
Small. 2023 May;19(18):e2207248. doi: 10.1002/smll.202207248. Epub 2023 Feb 1.
Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.
胶质母细胞瘤（GBM）是最常见的致命性脑肿瘤，治疗效果不佳，对化疗反应差。作为细胞遗传学和代谢的调节中心，大多数肿瘤化疗药物在核内发挥治疗作用。具有核聚集效应的纳米药物有望消除并从根本上抑制肿瘤细胞。在这项研究中，引入了一种基于多面体低聚倍半硅氧烷（POSS）的纳米药物递送系统，将药物递送至 GBM 细胞的核内，从而有效增强化疗的疗效。通过受体介导的内吞作用，用叶酸和 iRGD 肽分子对纳米颗粒进行修饰，以提高其对肿瘤细胞的靶向性和摄取。核聚集允许将化疗药物替莫唑胺（TMZ）直接递送至肿瘤细胞核内，从而导致更显著的 DNA 损伤和抑制肿瘤细胞增殖。载 TMZ 的 POSS 纳米颗粒可显著提高荷瘤小鼠的存活率。因此，经修饰的 POSS 纳米颗粒可用作有前途的载药递送平台，以改善 GBM 患者的化疗效果。
