Tianlong Liu

In our previous study we reported that the interaction of nanoparticles with cells can be influenced by particle shape, but until now the effect of particle shape on in vivo behavior remained poorly understood. In the present study, we control the fabrication of fluorescent mesoporous silica nanoparticles (MSNs) by varying the concentration of reaction reagents especially to design a series of shapes. Two different shaped fluorescent MSNs (aspect ratios, 1.5, 5) were specially designed, and the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. Organ distributions show that intravenously administrated MSNs are mainly present in the liver, spleen and lung (>80%) and there is obvious particle shape effects on in vivo behaviors. Short-rod MSNs are easily trapped in the liver, while long-rod MSNs distribute in the spleen. MSNs with both aspect ratios have a higher content in the lung after PEG modification. We also found MSNs are mainly excreted by urine and feces, and the clearance rate of MSNs is primarily dependent on the particle shape, where short-rod MSNs have a more rapid clearance rate than long-rod MSNs in both excretion routes. Hematology, serum biochemistry, and histopathology results indicate that MSNs would not cause significant toxicity in vivo, but there is potential induction of biliary excretion and glomerular filtration dysfunction. These findings may provide useful information for the design of nanoscale delivery systems and the environmental fate of nanoparticles.

Mesoporous silica nanomaterial is one of the most promising candidates as drug carrier for cancer therapy. Herein, in vitro and in vivo study of silica nanorattle (SN) with mesoporous and rattle-type structure as a drug delivery system was first reported. Hydrophobic antitumor drug docetaxel (Dtxl) was loaded into the PEGylated silica nanorattle (SN-PEG) with a diameter of 125 nm via electrostatic absorption. In human liver cancer cell Hep-G2, the half-maximum inhibiting concentration (IC(50)) of silica nanorattle encapsulated docetaxel (SN-PEG-Dtxl) was only 7% of that of free Dtxl at 72 h. In vivo toxicity assessment showed that both nanocarrier of silica nanorattle (40 mg/kg, single dose) and SN-PEG-Dtxl (20 mg/kg of Dtxl, three doses) had low systematic toxicity in healthy ICR mice. The SN-PEG-Dtxl (20 mg/kg, intravenously) showed greater antitumor activity with about 15% enhanced tumor inhibition rate compared with Taxotere on the marine hepatocarcinoma 22 subcutaneous model. The results prove that the SN-PEG-Dtxl has low toxicity and high therapy efficacy, which provides convincing evidence for the silica nanorattle as a promising candidate for a drug delivery system.

Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.