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Dual‐Targeting Lactoferrin‐Conjugated Polymerized Magnetic Polydiacetylene‐Assembled Nanocarriers with Self‐Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy
Author(s) -
Fang JenHung,
Chiu TsungLang,
Huang WeiChen,
Lai YenHo,
Hu ShangHsiu,
Chen YouYin,
Chen SanYuan
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500750
Subject(s) - nanocarriers , magnetic resonance imaging , in vivo , blood–brain barrier , drug delivery , materials science , lactoferrin , biophysics , targeted drug delivery , fluorescence lifetime imaging microscopy , curcumin , biomedical engineering , chemistry , nanotechnology , fluorescence , medicine , biochemistry , central nervous system , microbiology and biotechnology , physics , quantum mechanics , endocrinology , biology , radiology
Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood–brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood–brain barrier (BBB)‐crossing efficiency for brain tumor therapy, a new dual‐targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross‐linkable 10,12‐pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles‐polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self‐responsive fluorescence upon intracellular uptake for cell trafficking and imaging‐guided tumor treatment. The magnetic Lf‐modified PDNCs with magnetic resonance imaging (MRI) and dual‐targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf‐ Cur (Curcumin)‐PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur . Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain‐bearing rats.