Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles.

Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.

Contribution to in vitro screening of Egyptian plants for schistosomicidal activity.

CONTEXT: This study is a continuation of our previous work in which a bioassay screening of 346 methanol extracts from 281 Egyptian plant species was carried out for in vitro schistosomicidal activity. OBJECTIVE: Another 309 methanol extracts from 278 plant species were subjected to the bioassay screening using the same technique on viable Schistosoma mansoni Sambon (Schistosomatidae) mature worms in specialized culture medium (Roswell Park Memorial Institute medium 1640) in a trial to discover a source for a schistosomiasis drug from Egyptian flora. MATERIAL AND METHODS: The methanol plant extracts were tested in vitro against viable S. mansoni mature worms in culture medium. Viability of worms was examined after exposure to 100 µg/ml of the extract in the medium for 24 h. Negative (dimethyl sulfoxide) and positive (praziquantel) controls were simultaneously used. Extracts showing schistosomicidal activity were further subjected to determination of their (Lethal concentration) LC50 and LC90 values. RESULTS: Confirmed in vitro antischistosomal activity was found in 42 extracts. Of these, 14 plant species possessed considerably high antischistosomal activity (LC50 ≤ 15 µg/ml), viz. Callistemon viminalis (Soland. Ex Gaertn) Cheel, C. rigidus R.Br., C. speciosus (Sims.) DC, C. citrinus Stapf, Eucalyptus citriodora Hook, E. rostrata Dehnh., Eugenia edulis Vell, E. javanica Lam syn. Syzygium samarangense (Blume) Merril, Melaleuca leucadendron (L.) L., M. stypheloides Sm. (all belong to Myrtaceae), Cryptostegia grandiflora R.Br. (Asclepiadaceae), Zilla spinosa (L.) Prantl (Cruciferae), Ficus trijuja L. (Moraceae) and Fagonia mollis Delile (Zygophylacae). DISCUSSION AND CONCLUSION: These species may represent additional natural sources of bioactive material that deserve further investigation for drug discovery against schistosomiasis.