Unraveling the structure of innovative bio-based cubosomes

Glioblastoma (GBM) is one of the deathliest types of brain cancer due to its aggressive nature and limited treatment options, resulting in high mortality rates. Despite current therapies, including surgery, radiation, and chemotherapy, GBM prognosis remains low, with median survival rates of only 14 to 16 months. To address the shortcomings of existing treatments, there is growing interest in nanotechnology-based approaches, particularly the use of nanoparticles (NPs) for targeted drug delivery.

Membrane-coated NPs, which mimic the surface characteristics of cancer cells, show promise in enhancing tumor homologous targeting while evading immune recognition.
Liposomes have been extensively studied as suitable membrane-coated NPs, nevertheless, limitations in terms of production complexity, drug loading, and stability hinder their widespread clinical application. Cubosomes are a novel smart generation of lipid nanocarriers with higher stability and drug loading efficiency and less demanding production methods.
We developed a novel type of nanoparticle-based on innovative biomimetic monoolein-based cubosomes stabilized with GBM cell membranes for targeting and treating GBM. Cubosomes were loaded with two standard GBM drugs, 5-aminolevulinic acid (5-ALA) and temozolomide (TMZ), to improve therapeutic efficacy. To investigate the internal cubic structure of cubosomes, phase
symmetry, and study the occurrence of lipid rearrangements upon the incorporation of thestabilizers and loading of the two drugs, specific high-resolution techniques such as SAXS and WAXS are needed. This project aims to characterize the internal cubic structures of innovative monoolein-based cubosomes and investigate their properties when incorporating standard phospholipids (DPPC and DPPE) as stabilizers, as well as GBM cell membranes. Additionally, the study will assess the effects of loading two GBM drugs, 5-ALA and TMZ, into these cubosomes.

胶质母细胞瘤（Glioblastoma, GBM）是致死性最强的脑癌类型之一，因其侵袭性极强且可用治疗手段有限，死亡率居高不下。尽管现有疗法涵盖手术、放疗与化疗，但胶质母细胞瘤的预后仍极差，中位生存期仅为14至16个月。为弥补现有治疗手段的不足，基于纳米技术的疗法愈发受到关注，其中尤以用于靶向给药的纳米颗粒（nanoparticles, NPs）为研究热点。

模拟癌细胞表面特征的膜包被纳米颗粒，在增强肿瘤同源靶向性同时逃避免疫识别方面展现出应用潜力。脂质体作为一类被广泛研究的膜包被纳米颗粒，但其生产复杂度高、药物装载量有限且稳定性不足，阻碍了其临床大规模应用。立方体（Cubosomes）是一类新型智能脂质纳米载体，具备更高的稳定性与药物装载效率，且生产流程更为简便。

本研究开发了一类新型纳米颗粒，以创新性的仿生单油酰基甘油立方体为基础，采用胶质母细胞瘤细胞膜进行稳定化修饰，用于靶向治疗胶质母细胞瘤。我们将两种临床常用的胶质母细胞瘤治疗药物——5-氨基酮戊酸（5-aminolevulinic acid, 5-ALA）与替莫唑胺（temozolomide, TMZ）装载至立方体中，以提升治疗效果。为探究立方体的内部立方结构、相对称性，以及稳定剂加入与两种药物装载后脂质重排的发生情况，需采用小角X射线散射（Small-Angle X-ray Scattering, SAXS）与广角X射线散射（Wide-Angle X-ray Scattering, WAXS）等高分辨率表征技术。本项目旨在对新型单油酰基甘油立方体的内部立方结构进行表征，并探究其在掺入标准磷脂（二棕榈酰磷脂酰胆碱, DPPC）与二棕榈酰磷脂酰乙醇胺（DPPE）作为稳定剂，以及结合胶质母细胞瘤细胞膜后的特性变化。此外，本研究还将评估将5-ALA与TMZ两种胶质母细胞瘤治疗药物装载至此类立方体后的效果。