A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.
BACKGROUND
Magnetic nanoparticles (NPs) loaded with antitumor drugs in combination with an external magnetic field (EMF)-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1) to investigate application of PEG modified GMNPs (PGMNPs) as a drug carrier of the chemotherapy compound doxorubicin (DOX) in vitro; 2) to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs) using an EMF-guided delivery in vivo.


METHODS
First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues) was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M).


RESULTS
The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each p<0.05), following treatment for 33 days. The life span of tumor-bearing mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX were 74.8±9.95, 66.1±13.5, and 31.3±3.31 days, respectively (each p<0.05).


CONCLUSIONS
This simple and adaptive nanoparticle design may accommodate chemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.
The College of Life Sciences, Northwest University, Xi'an, China.
Xu
X
Chao
Zhuoli
Z
Zhang
Lili
L
Guo
Jingjing
J
Zhu
Mingli
M
Peng
Alphonsus J M
AJ
Vermorken
Wim J M
WJ
Van de Ven
Chao
C
Chen
Yali
Y
Cui
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D006046:Gold / Q000737:chemistry; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008280:Magnetics; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D016019:Survival Analysis; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011092:Polyethylene Glycols; D006046:Gold; D004317:Doxorubicin