Glycoligand-targeted core-shell nanospheres with tunable drug release profiles from calixarene-cyclodextrin heterodimers

Stable core–shell nanospheres self-assemble inwater from heterodimers combining a hydrophobic calix[4]arene moiety and a hydrophilic b-cyclodextrin head; their potential to encapsulate and provide sustained release of the anticancer drug docetaxel and undergo surface post-modification with glycoligands targeting the macrophage mannose receptor is discussed

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

Molecular determinants for cyclooligosaccharide-based nanoparticle-mediated effective siRNA transfection

Aim: To study the structural requirements that a cyclooligosaccharide-based nanoparticle must fulfill to be an efficient siRNA transfection vector. Materials & methods: siRNA protection from degradation by RNAses, transfection efficiency and the thermodynamic parameters of the nanoparticle/siRNA interactions were studied on pairs of amphiphilic molecules using biochemical techniques and molecular dynamics. Results: The lower the siRNA solvent accessible surface area in the presence of the nanoparticle, higher the protection from RNAse-mediated degradation in the corresponding nanocomplex; a moderate nanoparticle/siRNA binding energy value further facilitates reversible complexation and binding to the target cellular mRNA. Conclusion: The use, in advance, of these parameters will provide a useful indication of the potential of a molecular nanoparticle as siRNA transfecting vector

A Structure‐Activity Investigation on Modified Analogues of an Argininocalixarene Based Non‐viral Gene Vector

AbstractThe tetra‐L‐arginino‐tetrahexyloxycalix[4]arene 1 has shown extraordinary abilities to compact and internalize different types of Nucleid Acid cargos (DNA, microRNA, PNA) into cells even known to be transfected with great difficulties by commercial non‐viral gene delivery systems. This activity, accompanied by negligible toxicity, makes this calixarene a rather promising prototype of vector for Gene Therapy. In this study we report how small structural changes like i) the lower rim alkyl substituents, ii) the type of the terminal cationic headgroups (guanidinium or primary ammonium), iii) the length of the linker between the macrocycle and the terminal cationic headgroup, iv) the presence/absence of the basic α‐amino group of Arg, and v) the stereochemistry (L or D) of Arg, might affect the ability of the novel calixarene vectors to compact DNA and to deliver its cargo into the cells