Magnetic Core-Shell Nanocapsules with Dual-Targeting Capabilities and Co-Delivery of Multiple Drugs to Treat Brain Gliomas

• Published in: Advanced healthcare materials 2014-08, Vol.3 (8), p.1250-1260
• Main Authors: Fang, Jen-Hung, Lai, Yen-Ho, Chiu, Tsung-Lang, Chen, You-Yin, Hu, Shang-Hsiu, Chen, San-Yuan
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Brain; Brain Neoplasms - drug therapy; brain tumors; Cell Line, Tumor; Cell Survival - drug effects; Chemical industry; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - toxicity; double emulsion; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - toxicity; Drug delivery systems; Drug Therapy, Combination; Drugs; Emulsions; Female; Glioma - drug therapy; Humans; Magnetics; Magnetite Nanoparticles - chemistry; Medical research; Mice; Mice, Inbred BALB C; Mice, Nude; multiple drugs; Nanocapsules - chemistry; nanocarriers; Nanostructure; Particle Size; Polyvinyl alcohols; targeting; Therapy
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201300598

Lactoferrin (Lf)‐tethered magnetic double emulsion nanocapsules (Lf‐MDCs) are assembled from polyvinyl alcohol (PVA), polyacrylic acid (PAA), and iron oxide (IO) nanoparticles. The core–shell nanostructure of the Lf‐MDCs (particle diameters from 100 to 150 nm) can simultaneously accommodate a hydrophilic drug, doxorubicin (Dox), and a hydrophobic drug, curcumin (Cur), in the core and shell, respectively, of the nanocapsules for an efficient drug delivery system. The release patterns of the two drugs can be regulated by manipulating the surface charges and drug‐loading ratios, providing the capability for a stepwise adjuvant release to treat cancer cells. The results demonstrate that the dual (Dox+Cur)‐drug‐loaded nanocapsule can be effectively delivered into RG2 glioma cells to enhance the cytotoxicity against the cells through a synergistic effect. The combined targeting, i.e., magnetic guidance and incorporation of Lf ligands, of these Lf‐MDCs results in significantly elevated cellular uptake in the RG2 cells that overexpress the Lf receptor. Interestingly, an intravenous injection of the co‐delivered chemotherapeutics follows by magnetic targeting in brain tumor‐bearing mice not only achieve high accumulation at the targeted site but also more efficiently suppress cancer growth in vivo than does the delivery of either drug alone. Magnetic double emulsion capsules (MDCs) equipped with dual‐targeting modalities of lactoferrin and magnetic guidance can achieve the efficacious therapy and reduce the side effect by enhancing the cumulative amount and cell internalization. Once MDCs entrapped in lysosome, doxorubicin, and curcumin can be simultaneously released to overcome multidrug resistance and inhibit the tumor growth of brain glioma through synergistic therapy.