Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.

The objective of the present study was to investigate the specific drug targeting of anticarcinogenic drugs, such as camptothecin (CA), after intravenous (i.v.) injection by incorporation into solid lipid nanoparticles (SLN). A CA loaded SLN suspension consisted of 0.1% (w/w) camptothecin, 2.0% (w/w) stearic acid, 1.5% (w/w) soybean lecithin and 0.5% (w/w) polyoxyethylene-polyoxypropylene copolymer (Poloxamer 188) was prepared by high pressure homogenization. In vitro drug release was investigated in pH 7.4 phosphate-buffered saline at 37 degrees C. The concentrations of camptothecin in various organs were determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after i.v. administration of CA-SLN and a camptothecin control solution (CA-Sol). The results showed that the CA-SLN had an average diameter 196.8 nm with a Zeta potential of -69.3 mV and in vitro drug release was achieved for up to a week. In tested organs, the AUC/dose and the mean residence times (MRT) of CA-SLN were much higher than those of CA-Sol, especially in brain, heart and reticuloendothelial cells containing organs. The brain AUC ratio of CA-SLN to CA-Sol was the highest among the tested organs. These results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity.