Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment.
Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment.
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DOI：
10.1016/j.nano.2022.102581
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发表时间：
2022-07
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通讯作者：
Zhang Ye;Lun Gao;Jiayang Cai;Yixuan Wang;Yong Li;Shi’ao Tong;Tengfeng Yan;Qian Sun;Yangzhi Qi;Yang Xu;Hongxiang Jiang;Si Zhang;Linyao Zhao;Shenqi Zhang;Qianxue Chen
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文献类型：
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作者：
Zhang Ye;Lun Gao;Jiayang Cai;Yixuan Wang;Yong Li;Shi’ao Tong;Tengfeng Yan;Qian Sun;Yangzhi Qi;Yang Xu;Hongxiang Jiang;Si Zhang;Linyao Zhao;Shenqi Zhang;Qianxue Chen
多形性胶质母细胞瘤（GBM）是发病率和死亡率最高的颅内恶性肿瘤。由于血脑屏障（BBB）的存在，化疗通常对GBM无效;然而，纳米技术的应用有望克服这一限制。聚乳酸-羟基乙酸共聚物（PLGA）是一种可降解、无毒、生物相容性好的功能高分子材料，广泛应用于医药行业。以前的研究表明，PLGA纳米颗粒（NP）穿透血脑屏障的能力在很大程度上取决于它们的大小;然而，最佳PLGA NP大小的确定需要进一步的研究。在这里，我们报告了一种基于tandutinib的前药（proTan），它响应GBM微环境，与NP结合以克服BBB。载有proTan的AMD 3100-PLGA纳米粒抑制肿瘤生长，并有效延长荷瘤小鼠的生存期。
Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood–brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.