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Nanoparticles Surmounting Blood–Brain Tumor Barrier Through Both Transcellular and Paracellular Pathways to Target Brain Metastases
Author(s) -
Miao Tongtong,
Ju Xiufeng,
Zhu Qiuning,
Wang Yamei,
Guo Qian,
Sun Tao,
Lu Chunzhu,
Han Liang
Publication year - 2019
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201900259
Subject(s) - paracellular transport , transcellular , brain metastasis , blood–brain barrier , transcytosis , doxorubicin , brain tumor , cancer research , extravasation , nanomedicine , tight junction , medicine , hyaluronic acid , tumor microenvironment , drug delivery , metastasis , chemotherapy , pharmacology , pathology , materials science , biology , endocytosis , central nervous system , cancer , nanoparticle , nanotechnology , biophysics , microbiology and biotechnology , receptor , tumor cells , permeability (electromagnetism) , membrane , genetics , anatomy
Brain metastases are one of the most difficult malignancies to treat owing to their location and mostly multifocal and infiltrative growth. Chemotherapy, which is often effective against tumors outside the brain, offers some hope for brain metastases. However, the efficacy of systemic drug delivery to brain metastases is extremely limited due largely to the blood–brain tumor barrier (BTB). Herein, it is reported that minoxidil‐loaded hyaluronic acid–tethered nanoparticles (M@H‐NPs) can efficiently and specially surmount the BTB through both transcellular and paracellular pathways and target brain metastases through coordination of hyaluronic acid with CD44 target. The transcellular endocytosis, paracellular claudin‐5 expression, and BTB crossing are evaluated to confirm that the developed M@H‐NPs can be endued with minoxidil's ability to boost transcytosis and downregulate tight junction protein in BTB endothelial cells at brain metastases for promoted BTB penetration. M@H‐NPs selectively deliver doxorubicin (DOX) to brain metastatic lesions, while sparing normal brain cells from harm. Treatment with M@H‐NPs/DOX significantly prolongs median survival of mice bearing brain metastases. Due to the fruitful BTB penetration and brain metastasis homing, and improved therapeutic outcome, the minoxidil‐based systemic drug delivery strategy may serve as a potential approach for clinical management of brain metastases.