title: Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300, Taiwan.
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Fang
authors.affiliation: Department of Neurosurgery, Tzu Chi General Hospital, Tzu Chi University, Hualien, 970, Taiwan.
authors.forename: Tsung-Lang
authors.initials: TL
authors.lastname: Chiu
authors.affiliation: Department of Materials Science and Engineering, Carnegie Mellon University, No. 5000 Forbes Avenue, Wean Hall 3325, Pittsburgh, PA, 15213, USA.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Road, Hsinchu, 300, Taiwan.
authors.forename: Yen-Ho
authors.initials: YH
authors.lastname: Lai
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300, Taiwan.
authors.forename: Shang-Hsiu
authors.initials: SH
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, National Yang Ming University, Sec. 2, Linong Street, Taipei, 112, Taiwan.
authors.forename: You-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Road, Hsinchu, 300, Taiwan.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy; D007781:Lactoferrin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D000078789:Polyacetylene Polymer; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D053279:Polyynes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D000078789:Polyacetylene Polymer; D011108:Polymers; C000499:ferric oxide; D053279:Polyynes; C082361:polydiacetylene; D007781:Lactoferrin; D003474:Curcumin
keywords: blood-brain barrier; lactoferrin (Lf); magnetic nanocarriers; superparamagnetic iron oxide (SPIO)