近红外激活的仿生纳米平台用于肿瘤特异性药物释放、穿透及正位胶质母细胞瘤的化学-光热协同治疗
Near Infrared-Activatable Biomimetic Nanoplatform for Tumor-Specific Drug Release, Penetration and Chemo-Photothermal Synergistic Therapy of Orthotopic Glioblastoma
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影响因子:6.5
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Ming Li, Xinrui Zhang, Yujie Zhou, Yuteng Chu, Jie Shen, Yue Cai, Xuanrong Sun
DOI:
10.2147/IJN.S466268
摘要
胶质母细胞瘤（Glioblastoma multiforme, GBM）是一种高度侵袭性且预后困难的脑肿瘤，由于血脑屏障（BBB）的存在以及深部肿瘤病灶中药物积聚的难度，治疗面临重大挑战。我们提出了一种仿生纳米平台，利用修饰有angiopep-2的巨噬细胞膜，载有吲哚菁绿（ICG），通过自组装形成SN38（AM-NP），实现主动肿瘤靶向和血脑屏障的有效穿透，依赖于特异性配体-受体相互作用。在积累于肿瘤部位后，这些纳米粒子通过激光照射和SN38的释放，诱导协同的化学-光热治疗。与缺乏细胞膜包封的裸纳米粒子（NP）相比，AM-NPs显著抑制肿瘤生长、明显提高存活率，并表现出优良的生物相容性和最小的副作用。这种近红外激活的仿生膜仿制巨噬细胞的纳米粒子增强了药物递送的靶向能力，通过修饰巨噬细胞膜和特异性配体，实现了协同的化学-光热治疗，显著提升了治疗效果。相比传统治疗手段，它提供了一种精准、高效、协同的治疗新策略，有望推动胶质母细胞瘤治疗的发展。
Abstract
Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects.This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.