Fruit‐Derived Extracellular‐Vesicle‐Engineered Structural Droplet Drugs for Enhanced Glioblastoma Chemotherapy

Abstract

Existing solid nanoparticle‐based drug delivery systems remain a great challenge for glioblastoma chemotherapy due to their poor capacities in crossing the blood‐brain barrier/blood‐brain tumor barrier (BBB/BBTB). Herein, we demonstrated fruit‐derived extracellular vesicles (EVs)‐engineered structural droplet drugs (ESDD) by programming the self‐assembly of fruit‐derived EVs at the DOX@squalene‐PBS interface, greatly enhancing the antitumor efficacy against glioblastoma. The EVs‐engineered structural droplet drugs experience a flexible delivery via deformation‐amplified macropinocytosis and membrane fusion, enabling them to highly efficiently cross BBB/BBTB and deeply penetrate glioblastoma tissues. As expected, the EVs‐engineered structural droplet drugs exhibited 2.5‐fold intracellular uptake, 2.2‐fold transcytosis, and 5‐fold membrane fusion as higher as the EVs (cRGD modified), allowing the highly efficient accumulation, deep penetration, and cellular internalization into the glioblastoma tissues and thereby significantly extending the survival time of glioblastoma mice.This article is protected by copyright. All rights reserved

Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine

“…In addition, Fan’s research group also programmed the self-assembly of fruit-derived EVs modified with the tumor-targeting peptide cRGD on the DOX@squalene-PBS interface, allowing structured droplet drugs designed based on EVs to amplify macropinocytosis through deformation and membrane fusion for flexible delivery, and to efficiently cross the BBB/BBTB and penetrate deeply into glioblastoma tissue ( Figure 4 ). 80 Besides, the immobilization of ligands on the surface of PDVs could be used for bioimaging. For example, Zhuang et al reported the use of lipophilic carbocyanine dyes to label grapefruit-derived nanocarriers and track the distribution in vivo by fluorescence.…”

Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants

“…The transfer of these PDEV-loaded bioactive compounds can significantly impact the biological behaviors of recipient cells, particularly those related to various diseases like tumors and inflammation. Recent research has demonstrated that multiple PDEVs possess the ability to withstand challenging conditions in the gastrointestinal tract and overcome biological obstacles (Liu et al, 2023). It suggests that PDEVs may have great promise as platforms for delivering drugs.…”

“…Besides inherent biological activities, PDEVs could be engineered as desired drug delivery platforms for the precise delivery of poorly soluble agents or therapeutic compounds, such as surface functionalization and content modification. Recent studies have focused on modification techniques to improve the drug delivery precision and efficiency of PDEVs (Chen et al, 2023).…”

Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood–Brain Barrier

“…A significant area of research on MSNs involves the application of PEGylation strategies. These strategies explore the impact of PEG’s molecular weight and density on factors such as blood circulation, degradation, hemolysis, and mucosal penetration. , Crucially, efforts have been made to integrate PEGylation with active targeting ligands, enhancing the ability of MSNs to specifically target brain tumors. , This dual approach of customizing both the internal (pores) and external surfaces of MSNs allows for precise control over drug loading and the pharmacokinetics (PKs) of the delivered payloads. While MSNs share a similar concept of nanocarriers with other NPs, the “distinctive mesoporous scaffolds,” “facades,” and “interior designs” can be fine-tuned, offering specialized utilities …”

“… 25 , 26 Crucially, efforts have been made to integrate PEGylation with active targeting ligands, enhancing the ability of MSNs to specifically target brain tumors. 28 , 29 This dual approach of customizing both the internal (pores) and external surfaces of MSNs allows for precise control over drug loading and the pharmacokinetics (PKs) of the delivered payloads. While MSNs share a similar concept of nanocarriers with other NPs, the “distinctive mesoporous scaffolds,” “facades,” and “interior designs” can be fine-tuned, offering specialized utilities.…”