Existing nanoparticle-mediated drug delivery systems for glioma systemic chemotherapy remain a great challenge due to poor delivery efficiency resulting from the blood brain barrier/blood-(brain tumor) barrier (BBB/BBTB) and insufficient tumor penetration. Here, we demonstrate a distinct design by patching doxorubicin-loaded heparin-based nanoparticles (DNs) onto the surface of natural grapefruit extracellular vesicles (EVs), to fabricate biomimetic EV-DNs, achieving efficient drug delivery and thus significantly enhancing antiglioma efficacy. The patching strategy allows the unprecedented 4-fold drug loading capacity compared to traditional encapsulation for EVs. The biomimetic EV-DNs are enabled to bypass BBB/BBTB and penetrate into glioma tissues by receptor-mediated transcytosis and membrane fusion, greatly promoting cellular internalization and antiproliferation ability as well as extending circulation time. We demonstrate that a high-abundance accumulation of EV-DNs can be detected at glioma tissues, enabling the maximal brain tumor uptake of EV-DNs and great antiglioma efficacy in vivo.

中文翻译：

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通过整合葡萄柚细胞外囊泡和阿霉素负载的肝素基纳米颗粒的仿生药物传递系统，用于神经胶质瘤治疗

由于由血脑屏障/血液-（脑肿瘤）屏障（BBB / BBTB）引起的递送效率差以及肿瘤​​渗透不足，用于神经胶质瘤全身化学疗法的现有纳米粒子介导的药物递送系统仍然是巨大的挑战。在这里，我们通过将载有阿霉素的肝素基纳米颗粒（DNs）修补到天然葡萄柚细胞外囊泡（EVs）的表面上，以制造仿生EV-DNs，实现有效的药物输送，从而显着提高抗神经胶质瘤的功效，从而展示了独特的设计。与传统的EV封装相比，修补策略可实现前所未有的4倍载药量。仿生EV-DNs可通过受体介导的胞吞作用和膜融合作用绕过BBB / BBTB并渗透到神经胶质瘤组织中，极大地促进了细胞内在化和抗增殖能力，并延长了循环时间。我们证明，可以在神经胶质瘤组织中检测到大量的EV-DN积累，从而可以最大程度地吸收EV-DN的脑肿瘤并在体内具有很大的抗神经胶质瘤功效。