Management of glioblastoma multiforme (GBM), a cerebral glioma with highest-grade malignancy, is a crucial challenge to current anticancer treatment because the lack of GBM-targeting capability of antitumor drug, such as carmustine (BCNU) with a short half-life, along with low blood-brain barrier (BBB) permeability to achieve the clinical efficacy. Hence, polyethyleneimine-poly(lactic-co-glycolic acid) nanoparticles comprising stable core-shell structure with tamoxifen were crosslinked with sialic acid (SA-TAM-PEI-PLGA NPs) as nanocarriers to improve bioavailability of BCNU for pharmacotherapy. The brain-targeted experiments revealed that an increasing SA level improved BBB permeability for BCNU, and was associated with a reduction in transendothelial electrical resistance and an increase in propidium iodide penetration of endothelial monolayer. Immunocytochemical staining images evidenced that surface SA was critical in triggering transcytosis through N-acetylglucosamine on human cerebral microvessel endothelia, and surface crosslinking restrained macrophage phagocytosis. A high TAM level on the carrier surface reduced the survival rate of human U87, and western blots showed that conjugated TAM induced apoptosis of the cancer cells. The use of SA-TAM-PEI-PLGA NPs carrying BCNU as a pharmaceutical preparation is an effective strategy to overcome the BBB restriction and activate apoptosis of tumor cells to prevent the proliferation of GBM.

多形性胶质母细胞瘤（GBM）是一种具有最高恶性程度的脑胶质瘤，对于目前的抗癌治疗而言，这是一项至关重要的挑战，因为它缺乏针对GBM的抗肿瘤药物（如卡马汀（BCNU），半衰期短）的靶向能力，以及低血脑屏障（BBB）渗透性以达到临床疗效。因此，将包含稳定的具有他莫昔芬的核-壳结构的聚乙烯亚胺-聚（乳酸-乙醇酸共聚物）纳米粒子与唾液酸（SA-TAM-PEI-PLGA NP）交联，以提高BCNU用于药物治疗的生物利用度。以大脑为目标的实验表明，SA含量的增加可提高BCNU的BBB渗透性，并与内皮电阻降低和内皮单层碘化丙啶渗透增加有关。免疫细胞化学染色图像证明，表面SA在触发N-乙酰氨基葡萄糖对人脑微血管内皮细胞的转胞作用至关重要，并且表面交联抑制了巨噬细胞的吞噬作用。载体表面的高TAM水平降低了人U87的存活率，并且蛋白质印迹显示缀合的TAM诱导了癌细胞的凋亡。使用带有BCNU的SA-TAM-PEI-PLGA NP作为药物制剂是克服BBB限制并激活肿瘤细胞凋亡以阻止GBM增殖的有效策略。载体表面的高TAM水平降低了人U87的存活率，并且蛋白质印迹显示缀合的TAM诱导了癌细胞的凋亡。使用带有BCNU的SA-TAM-PEI-PLGA NP作为药物制剂是克服BBB限制并激活肿瘤细胞凋亡以阻止GBM增殖的有效策略。载体表面的高TAM水平降低了人U87的存活率，并且蛋白质印迹显示缀合的TAM诱导了癌细胞的凋亡。使用带有BCNU的SA-TAM-PEI-PLGA NP作为药物制剂是克服BBB限制并激活肿瘤细胞凋亡以阻止GBM增殖的有效策略。