Juan Wu, Wei Jiang, Fengsheng Li, Yewen Shen, Wei Jiang and Renbing Tian
Nanjing University of Science and Technology, China
Posters & Accepted Abstracts: Med chem
The development of tumor specific multifunctional nanoparticles for targeted and efficient delivery of drugs to tumor cells is currently an area of intense research with the potential to revolutionize the treatment of cancer. As a major class of nanoparticles, magnetic iron oxide nanoparticles have been examined extensively for applications in cancer therapy due to their ultra-fine size, biocompatibility and magnetic properties. In addition, the pH value of most solid tumors (pH<6.0) was lower than the surrounding normal tissues (pH 7.4). Therefore, in our work, we developed and prepared two different Fe3O4- based doxorubicin (DOX) delivery systems and the drug loading modes were chemical bond (system I) and electrostatic adsorption (system II), respectively. In system I, Fe3O4 nanoparticles were coated by polyethyleneglycol (PEG) used as surfacemodifying agent and polyethyleneimine (PEI) used as the drug-loading site via a one-pot pyrolysis method. The prepared carriers were within 20 nm and had good stability in dispersion and super-paramagnetic properties. DOX was grafted to PEG/PEI@Fe3O4 at a loading rate of up to 85% via the reaction between the 13-carbonyl of DOX and the primary amine of PEI. During in vitro release studies, nearly 81% DOX was released from the system within 72 h at pH 4.5, compared with only 28% at pH 7.4. For system II, DOX was loaded onto recyclable clusters of Fe3O4 nanoparticles at a loading rate of 76.19% by electrostatic interaction which has desirable pH-responsivity usually exhibits easier operation in experimental procedure, and lower consumption and pollution. Moreover, the release studies in vitro showed that the system II had excellent pH-sensitivity, 76.16% of DOX was released within 72 h at pH 4.0, and the secondary drug loading rate was nearly 52%. WST-1 assays in model breast cancer cells (MCF-7) demonstrated that system II exhibited high anti-tumor activity, while the recyclable clusters of Fe3O4 nanoparticles were practically non-toxic. Our results revealed that both system I and system-II would be a competitive candidate for targeted cancer therapy in the near future. While in the case of the little difference of drug loading rate and the release rate between system I and system II, the latter would be even better due to its environmentally friendly drug loading mode and the recyclable drug loading performance.
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