Preparation And Application Of Doxorubicin Conjugated Gold Nanoparticles For Nano Drug Carriers

Nano drug carriers have been used in the treatment of cancer cells for its inherent advantages. Compared to the traditional drugs having the single function, nano drug carriers could combine the advantages of different components, making it versatile with stability, targeting, imaging and controlled drug release.Gold nanoparticles as an inorganic materials, has many fundamental advantages, such as good biocompatibility, low toxicity, and ease of surface function. Due to its unique physical, chemical and optical properties, the nano drug carriers based on gold nanoparticles have been widely used in recent years for medical imaging and cancer treatment. In this study, we synthesized gold nano drug carriers with doxorubicin (DOX) as anti-cancer drug for the treatment and imaging of cancer cells. The details are shown as followings.1. Novel pH-sensitive gold nanoparticles (Au NPs) with folate targeting and fluorescence storage (DL-Au-LPF NPs) were synthesized from simultaneously conjugating lipoic acid (LA) modified DOX (LA-DOX) and LA modified polyethylene glycol with folate acid (LA-PEG-FA) onto the surface of Au NPs. LA-DOX with hydrazone linkage offered pH sensitive and LA-PEG-FA offered the folate-targeted property, meanwhile, the fluorescence storage was achieved due to the nanosurface energy transfer (NSET) between Au NPs and the fluorescent DOX. The composition, morphology, and properties of the as-prepared composites were characterized by1H NMR spectroscopy, FTIR spectroscopy, UV-Visible spectroscopy, transmission electron microscopy (TEM) and fluorescence spectroscopy. DOX with an upload ratio of4.9%had significantly higher release rate at mildly acidic pH5.0, compared to physiological pH7.4, and had a maximum cumulative release ratio up to81%. Cellular uptake and cytotoxicity studies indicated that these DL-Au-LPF NPs were easily internalized by living cells, mainly due to the folate-receptor mediated endocytosis mechanism and further led to higher anticancer efficacy. The cytotoxicity study also indicated that DL-Au-LPF NPs had very high toxicity toward cancer cells, while the controlled L-Au-LPF NPs had little toxicity. All these results suggested that DL-Au-LPF NPs could be used as multifunctional nano drug carriers with pH-sensitive, fluorescence storage and tumor-targeted properties.2. Smart nano drug carriers of MSNs@DOX@Au were synthesized with mesoporous silica (MSNs) as the adsorbents of anti-cancer drug DOX and ultra small Au NPs as plugging holes agent. The composition, morphology, and properties of the as-prepared composites were characterized by elemental analysis, fluorescence spectroscopy, FTIR spectroscopy, TEM, nitrogen adsorption-desorption, thermal gravimetric and UV-visible spectroscopy. In vitro release experiments showed that under simulated conditions of endosome pH5.0-6.0and GSH10mM, Au NPs could escape from the surface of MSNs, which promoted the release of DOX from mesoporous to the external environment, and the highest release ratio of DOX was56.43%. While under the physical environment pH7.4, since the mesoporous had been closed, DOX could not release and the release ratio was only6.68%. These smart nano drug carriers could effectively avoid the drug leaked and ensure the security of MSNs@DOX@Au acted as nano drug carriers. The cytotoxicity and imaging studies also indicated that DOX@MSNs@Au had high growth inhibition toward Tca8113cells and had sustained release ratio of DOX with an effective drug concentration.