Glioma-targeted dual functionalized thermosensitive Ferri-liposomes for drug delivery through an in vitro blood-brain barrier.

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ID: 17157
2019
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Abstract
To date, the delivery of therapeutic agents for malignant brain tumors (such as glioblastoma multiforme (GBM)) remains a significant obstacle due to the existence of the blood-brain barrier (BBB). A multitude of delivery systems (hydrogels, micelles, polymeric nanoparticles, etc.) have been proposed, yet many of them exhibit limited tumor-specific inhibition effects. Herein, a drug-encapsulated dual-functionalized thermosensitive liposomal system (DOX@P1NS/TNC-FeLP) was developed for targeted delivery across the BBB. Specifically, a GBM-specific cell-penetrating peptide (P1NS) and an anti-GBM antibody (TN-C) were conjugated onto the liposome surface for targeted delivery. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin (DOX) were co-loaded inside the liposomes to achieve thermo-triggered drug release when applying an alternating magnetic field (AMF). Results demonstrated that P1NS/TNC-FeLPs readily transported across an in vitro BBB model and displayed a thermo-responsive and GBM-specific cellular uptake as well as drug release profile. Additionally, results from immunofluorescent (IF) staining and RT-qPCR further demonstrated that DOX@P1NS/TNC-FeLPs specifically entered U-87 human GBM cells and suppressed tumor cell proliferation without causing any significant impact on healthy brain cell function. As such, the novel DOX@P1NS/TNC-FeLPs presented potent and precise anti-GBM capability and, therefore, are suggested here for the first time as a promising DDS to deliver therapeutic agents across the BBB for GBM treatment.
Reference Key
shi2019gliomatargetednanoscale Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Shi, Di;Mi, Gujie;Shen, Yan;Webster, Thomas J;
Journal Nanoscale
Year 2019
DOI
10.1039/c9nr03931g
URL
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