Dual-Targeting Magnetic PLGA Nanoparticles for Codelivery of Paclitaxel and Curcumin for Brain Tumor Therapy.
Chemotherapy is one of the most important strategies for glioma treatment. However, the "impermeability" of the blood-brain barrier (BBB) impedes most chemotherapeutics from entering the brain, thereby rendering very few drugs suitable for glioma therapy, letting alone application of a combination of chemotherapeutics. Thereby, there is a pressing need to overcome the obstacles. A dual-targeting strategy was developed by a combination of magnetic guidance and transferrin receptor-binding peptide T7-mediated active targeting delivery. The T7-modified magnetic PLGA nanoparticle (NP) system was prepared with co-encapsulation of the hydrophobic magnetic nanoparticles and a combination of drugs (i.e., paclitaxel and curcumin) based on a "one-pot" process. The combined drugs yielded synergistic effects on inhibition of tumor growth via the mechanisms of apoptosis induction and cell cycle arrest, displaying significantly increased efficacy relative to the single use of each drug. Dual-targeting effects yielded a >10-fold increase in cellular uptake studies and a >5-fold enhancement in brain delivery compared to the nontargeting NPs. For the in vivo studies with an orthotopic glioma model, efficient brain accumulation was observed by using fluorescence imaging, synchrotron radiation X-ray imaging, and MRI. Furthermore, the antiglioma treatment efficacy of the delivery system was evaluated. With application of a magnetic field, this system exhibited enhanced treatment efficiency and reduced adverse effects. All mice bearing orthotopic glioma survived, compared to a 62.5% survival rate for the combination group receiving free drugs. This dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.|Key Laboratory of Primate Neurobiology, Institute of Neuroscience, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences , 320 Yueyang Road, Shanghai 200031, China.
Yanna
Y
Cui
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
Meng
M
Zhang
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.|Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|Institute of Tropical Medicine, Guangzhou University of Chinese Medicine , 12 Jichang Road, Guangzhou 501405, China.
Feng
F
Zeng
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
Hongyue
H
Jin
Institute of Tropical Medicine, Guangzhou University of Chinese Medicine , 12 Jichang Road, Guangzhou 501405, China.
Qin
Q
Xu
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
Yongzhuo
Y
Huang
D000818:Animals; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D003474:Curcumin; D016503:Drug Delivery Systems; D005910:Glioma; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D017239:Paclitaxel; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin; D017239:Paclitaxel
PLGA nanoparticles; T7 peptide; brain targeting delivery; curcumin; magnetic targeting; paclitaxel