用于胶质母细胞瘤特异性靶向治疗的外泌体包被普鲁士蓝纳米颗粒
Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma.
作者信息
Hill Meghan L, Chung Seock-Jin, Woo Hyun-Joo, Park Cho Rong, Hadrick Kay, Nafiujjaman Md, Kumar Panangattukara Prabhakaran Praveen, Mwangi Leila, Parikh Rachna, Kim Taeho
出版信息
ACS Appl Mater Interfaces. 2024 Apr 10;16(16):20286-301. doi: 10.1021/acsami.4c02364.
Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.
胶质母细胞瘤是最具侵袭性的脑癌类型之一,5年生存率为6.8%。由于治疗选择有限,患者的生活质量往往较差,确诊后通常会转入姑息治疗。因此,迫切需要一种新的诊疗方法,以实现早期诊断和非侵入性治疗,因为目前基于肽的递送标准可能存在脱靶效应。普鲁士蓝纳米颗粒(PBNPs)最近被研究用作光声成像(PAI)和光热消融剂。然而,由于它们无法穿过血脑屏障(BBB),其在胶质母细胞瘤治疗中的应用受到限制。通过利用一种由PBNP内部和U-87癌细胞衍生的外泌体涂层(Exo:PB)组成的混合仿生纳米颗粒,我们展示了其在脑内的肿瘤特异性靶向作用以及由于强大的光转换能力而具有的选择性热疗潜力。对颗粒进行了表征,结果显示PBNPs周围有完整的涂层,其中含有外泌体标记物。细胞摄取模式与天然U-87外泌体相似,当暴露于808 nm激光时,在指定区域内显示出局部细胞死亡。将Exo:PB静脉注射到皮下植入胶质母细胞瘤的小鼠体内后,与聚乙二醇包被的PBNPs(PEG:PB)相比,它们显示出对肿瘤体积的有效靶向和消除作用。通过将Exo:PB颗粒全身给药到原位胶质母细胞瘤荷瘤小鼠体内,通过PAI在脑肿瘤区域检测到了PBNP信号。可以看出,与RGD:PB对照相比,Exo:PB具有优先的肿瘤蓄积且脱靶较少。通过苏木精和伊红染色(H&E)以及Ki67标记对Exo:PB与肿瘤的直接叠加进行分析,验证了特异性靶向作用。总体而言,我们开发了一种新型仿生材料,它可以自然穿过血脑屏障,并作为一种诊疗剂用于胶质母细胞瘤组织的全身靶向和光热治疗效果。