A Biomimetic Drug Delivery System by Integrating Grapefruit Extracellular Vesicles and Doxorubicin-Loaded Heparin-Based Nanoparticles for Glioma Therapy

• DOI: 10.1021/acs.nanolett.0c04753
• Publication Date: 2021-01-21T19:25:33Z
• Authors: Wenbo Niu; Qian Xiao; Xuejiao Wang; Junqiao Zhu; Jinheng Li; Xiaomei Liang; Yingming Peng; Chentian Wu; Ruojing Lu; Yao Pan; Jiamao Luo; Xinxian Zhong; Haoqi He; Zhili Rong; Jun-Bing Fan; Ying Wang
• Keywords: Transcytosis; Internalization; Targeted drug delivery

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