Tumor selectivity of stealth multi-functionalized superparamagnetic iron oxide nanoparticles

Caixia Fan, Wenhui Gao, Zhixi Chen, Hongyan Fan, Mingyan Li, Fengjun Deng, Zhiliang Chen
International Journal of Pharmaceutics 2011 February 14, 404 (1-2): 180-90
Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have traditionally been used as MRI contrast agent for disease imaging via passive targeting. However, there has been an increasing interest in the development of SPIO-NPs to cellular-specific targeting for imaging and drug delivery currently. The objective of our study was to develop a novel active tumor-targeting SPIO-NPs system by surface-modifying superparamagnetic iron oxide nanoparticles (SPIO-NPs) with o-carboxymethyl chitosans (OCMCS) and folic acid (FA) to improve their biocompatibility and ability to target specific tumor cells as well as to evade reticuloendothelial system (RES). The results in vitro indicated the covalent surface-modification of SPIO-NPs with OCMCS significantly reduced not only the nano-cytotoxicity but also the capture of SPIO-NPs by macrophage cells. On the other hand, the folic acid modification promoted the uptake of nanoparticles by FR-positive tumor cell lines, but had little impact on other cells without folate receptor (FR). MRI image and tumor histological analysis demonstrated the FA-OCMCS-SPIO-NPs had the ability to target tumor cells with FR in vivo. OCMCS and folic acid modification of SPIO-NPs could significantly improve both the SPIO-NPs biocompatibility and the FR target for MRI imaging, potential carrier for drug targeting and hyperthermia.

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