Synthesis, self-assembly and anticancer drug encapsulation and delivery properties of cyclodextrin-based giant amphiphiles.
Cyclodextrin-calixarene giant amphiphiles that can self-assemble into nanospheres or nanovesicles have the ability to encapsulate the anticancer hydrophobic drugs docetaxel, temozolomide and combretastatin A-4 with encapsulation efficiencies >80% and deliver them to tumoral cells, enhancing their therapeutic efficacy by 1-3 orders of magnitude. These amphiphiles were modified by inserting a disulfide bridge confering them redox responsiveness. Disassembly of the resulting nanocompounds and cargo release was favored by high glutathione levels mimicking those present in the tumor microenvironment. Anticancer drug-loaded nanoformulations inhibited prostate, breast, glioblastoma, colon or cervix cancer cell lines proliferation with IC50 values markedly below those observed for the free drugs. Cell-cycle analysis indicated a similar mechanism of action for drug-loaded nanocompounds and free drugs. The results strongly suggest that the cyclodextrin-calixarene heterodimer prototype is an excellent scaffold for nanoformulations aimed to deliver anticancer drugs with limited bioavailability due to low solubility to tumoral cells, markedly increasing their effectivity.
['Gallego-Yerga|Laura|L|', 'de la Torre|Cristina|C|', 'Sansone|Francesco|F|', 'Casnati|Alessandro|A|', 'Mellet|Carmen Ortiz|CO|', 'García Fernández|José M|JM|', 'Ceña|Valentín|V|']
D000970:Antineoplastic Agents D001682:Biological Availability D047250:Calixarenes D045744:Cell Line, Tumor D049109:Cell Proliferation D003505:Cyclodextrins D004337:Drug Carriers D065546:Drug Liberation D006801:Humans D057927:Hydrophobic and Hydrophilic Interactions D054118:Nanospheres
drug encapsulation cancer Cyclodextrins calixarenes drug delivery mitosis inhibitors