Local targeted therapy of liver metastasis from colon cancer by galactosylated liposome encapsulated with doxorubicin.

Since regional drug administration enables to maintain a high drug concentration within tumors, we compared the plasma concentration and biodistribution of doxorubicin (Dox) from drug-loaded conventional liposomes by local or systemic administration. The results demonstrated that drug concentration was substantially improved in liver as well as a decrease in blood and other organs by spleen injection mimicking portal vein perfusion (regional administration). To further investigate the targeted therapeutic effect of galactosylated liposome encapsulated doxorubicin (Dox) by regional administration, liver targeting liposomes were prepared by incorporating galactosylated-DPPE to conventional liposomes. Liposome uptake and targeting were verified in vitro and in vivo by fluorescence microscopy and xenogen IVIS imaging system, respectively. The results showed that galactose targeted liposomes presented a stronger specific cell uptake by human hepatocellular carcinoma HepG2 cells compared to the non-targeted liposomes. In vivo fluorescence imaging showed that the intra-hepatic deposition of conventional and galactosylated liposomes via spleen injection was more than that via tail vein administration, and galactosylated liposomes had higher fluorescent intensity over conventional liposomes in the liver post spleen administration. The anti-tumor effect of various drug administration routes for both liposomal formulations was evaluated using a murine liver metastasis model of colon cancer. The results indicated that tumor progression in the liver and mesenteric lymph nodes was significantly suppressed by Dox-loaded galactosylated liposomes via spleen injection, while no significance was observed in non-targeted formulations. Our data indicated that local perfusion of galactosylated liposomal doxorubicin had a great promise for the treatment of liver metastasis from colon cancer.

Cytotoxicity and TNF-alpha secretion in RAW264.7 macrophages exposed to different fullerene derivatives.

Fullerene derivatives have been reported as potential nanomedicines, however the role of surface chemical modification on the biological effects remains unclear. In this study, five kinds of water soluble C60 derivatives with different surface chemical modification, C60-(OH)20 (HFD), C60-(beta-Ala)10.1 (AFD), C60-(Lys)8.7 (KFD), C60-(Arg)8.6 (RFD) and C60-(NH(CH2)2NH2)8.8 (NFD) were synthesized. Their cytotoxicity as well as TNF-alpha secretions were evaluated in RAW264.7 macrophage cell line. The results show that no significant cytotoxicity can be observed upon 24 h exposure to C60 derivatives at less than 50 microg/mL. However, higher concentration (> 100 microg/mL) of these C60 derivatives decreases the proliferation of RAW264.7. The cytotoxicity of these fullerene derivatives is probably through the apoptosis pathway, while the extent of cytotoxicity varies with the different surface charges. Higher celluar uptake of HFD was observed in RAW264.7 cells than AFD, which correlates with the more toxic effect of HFD over AFD. The secretion of cytokine tumor necrosis factor alpha (TNF-alpha) was determined to evaluate the immunostimulating activity of these fullerene derivatives. The data show that the fullerene derivatives with negative surface charges secrete more TNF-alpha, whereas derivatives with positive charges show insignificant effect. The possible influence of various surface charge property on the observed biological effects is discussed.

Synthesis of PEGylated fullerene-5-fluorouracil conjugates to enhance the antitumor effect of 5-fluorouracil.

Many drugs have been delivered by different types of nanoscale vehicles to enhance their therapeutic efficacy. 5-Fluorouracil (5FU) is a widely used antitumor drug, however its bioavailability still needs to be improved. Herein we synthesized a polyethylene glycol monomethylether-C(60)-5FU conjugate (mPEG-C(60)-5FU) and evaluated its antitumor efficacy in vitro. The results show that the inhibition abilities of mPEG-C(60)-5FU to the human breast cancer cell line MCF-7 and the human gastric carcinoma cell line BGC-823 are significantly higher than that of 5FU. The conjugate has good stability in murine serum for at least 24 h. Moreover, the PEGylated fullerene (mPEG-C(60)) vehicle is non-toxic to MCF-7 cells. These results demonstrate that mPEG-C(60) is an efficient vehicle for the delivery of 5FU.

Hydrogenated and fluorinated host-guest surfactants: complexes of cyclodextrins with alkanes and fluoroalkyl-grafted alkanes.

A novel type of surfactants named "host-guest surfactants" were designed and synthesized. The headgroup and hydrophobic tail of the new surfactants are connected by supramolecular interactions rather than covalent bonds. The inclusion complexes of a series of cyclodextrins (CDs) and alkanes/fluoroalkyl-grafted alkanes were synthesized and measured by surface tension, XRD, XPS, TGA, and NMR spectroscopy. The methyl-ß-CD/hexadecane complex showed surface activity relative to those conventional hydrogenated surfactants. For the inclusion complex of hydroxypropyl-α-CD/C(8)F(17)SO(2)NHC(8)H(17), the structure was locked by subtle intermolecular recognition, which ensured the surprising surface activity similar to common excellent fluorinated surfactants. This surfactant, which was fabricated from nonsurface-active even insoluble components, showed the prospect that its surface activity might also be destroyed by introducing appropriate small species to extrude the guest from the cavity.