Magnetic nanoparticles with a pH-sheddable layer for antitumor drug delivery.
A dually responsive nanocarrier with a multilayer core-shell architecture was prepared based on Fe3O4@SiO2 nanoparticles successively coated with poly(benzyl L-aspartate) (PBLA) and poly(ethylene glycol) (PEG) for the purpose of tumor specific drug delivery applications. In this system, PEG chains are connected to the surface via pH-sensitive benzoic-imine bonds and serve as a pH-sheddable hydrophilic corona. Meanwhile, the PBLA segments serve as a hydrophobic middle layer used to load the drugs via hydrophobic interactions. The Fe3O4@SiO2 nanoparticle functions as a superparamagnetic core used to direct the drug loaded nanocarrier to the target pathological site. The obtained materials were characterized with FT-IR, (1)H NMR, dynamic light scattering, zeta-potential, TEM, TGA, and hysteresis loop analysis. An anticancer drug doxorubicin (DOX) was selected as the model drug loaded into the nanocarrier, which was relatively stable under physiological conditions due to its neutral hydrophilic shell, and could quickly release the drug in response to increased acidity via shedding of the PEG shells through cleavage of the intermediate benzoic-imine bonds. Meanwhile, the neutral shell shedding would reveal a positively charged nanoparticle surface that is readily taken up by tumor cells. These pH- and magnetic-responsive nanoparticles showed significant potential for use in the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.
Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Jingjing
J
Wang
Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Chu
C
Gong
Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Yinong
Y
Wang
Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China. Electronic address: guolinwu@nankai.edu.cn.
Guolin
G
Wu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D041681:NIH 3T3 Cells; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
D000970:Antineoplastic Agents; D001547:Benzaldehydes; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C032175:benzaldehyde
Benzoic-imine bond; Drug delivery; Magnetic nanoparticle; Poly(benzyl L-aspartate); pH-sheddable layer