Cyclodextrin-Based Nanosystems as Drug Carriers for Cancer Therapy.

BACKGROUND AND OBJECTIVE: Cyclodextrins have been of great interest as excellent candidates for fabricating versatile nano-drug delivery systems due to their commercial availability, easy functionalization, low immunogenicity, biocompatibility and safety. The possibility of reversible inclusion complex formation between cyclodextrins and various guest molecules in association with versatile exclusive properties of cyclodextrins offer a route towards the fabrication of highly sophisticated nanostructures with enormous potential for cancer treatment. METHODS AND RESULTS: The current review discusses important recent advances in the fabrication and development of cyclodextrin-based nanostructures for cancer therapy. Firstly, the formation of inclusion complexes between cyclodextrin derivatives and anticancer compounds, as well as their application, are summarized. Secondly, the cyclodextrins -based nanosystems including cyclodextrin-containing polymers, cyclodextrin-based supramolecular necklaces, which consist of polyrotaxanes and polypseudorotaxanes and cyclodextrin based hydrogels accompanied by their applications in cancer treatment are highlighted. In the end, the future perspective of this field is discussed. CONCLUSION: Numerous investigations in this area pave the way for the flourishing of the next generation of nano-therapeutics towards enhanced cancer therapy.

Polymer-Graphene Nanoassemblies and their Applications in Cancer Theranostics.

BACKGROUND AND OBJECTIVE: Graphene-based nanomaterials have received increasing attention due to their unique physical-chemical properties including two-dimensional planar structure, large surface area, chemical and mechanical stability, superconductivity and good biocompatibility. On the other hand, graphene-based nanomaterials have been explored as theranostics agents, the combination of therapeutics and diagnostics. In recent years, grafting hydrophilic polymer moieties have been introduced as an efficient approach to improve the properties of graphene-based nanomaterials and obtain new nanoassemblies for cancer therapy. METHODS AND RESULTS: This review would illustrate biodistribution, cellular uptake and toxicity of polymergraphene nanoassemblies and summarize part of successes achieved in cancer treatment using such nanoassemblies. CONCLUSION: The observations showed successful targeting functionality of the polymer-GO conjugations and demonstrated a reduction of the side effects of anti-cancer drugs for normal tissues.

Controlled quercetin release from high-capacity-loading hyperbranched polyglycerol-functionalized graphene oxide.

PURPOSE: An efficient drug-delivery system was prepared based on graphene oxide using a facile and one-step strategy for controlling the release of anticancer drugs. METHODS: Fabrication of single-layer graphene oxide (GO) sheets was carried out by both modified and improved Hummers method. Biocompatible hyperbranched polyglycerol (HPG) was grafted on the surface of GO through the ring-opening hyperbranched polymerization of glycidol. Various ratios of GO and glycidol were used for polymer grafting. An anticancer drug, quercetin (Qu), was loaded into modified GO via noncovalent interactions. RESULTS: Polymer grafting on the surface of GO sheets was confirmed by results obtained from Fourier-transform infrared and Raman spectroscopy, thermogravimetric analysis, energy-dispersive X-ray and X-ray spectroscopy, scanning electron microscopy, and atomic force microscopy. It was revealed that polymerization increased d-spacing between the basal planes. In addition, as a hydrophilic polymer, HPG improved the stability and dispersion of GO sheets in biological solutions and endowed extra drug-loading capacity for the sheets. The effect of hyperbranched structure on drug loading and release was investigated by comparing drug loading and release for HPG-modified GO and linear PPO-modified GO. Our experiments indicated high drug-loading capacity (up to 185%), and excellent encapsulation efficiency (up to 93%) for HPG-GO compared to linear PO-grafted GO. The release profile of Qu under various pH levels exhibited controlled and sustained drug release without an initial burst effect for HPG-GO, suggesting that an acidic solution could facilitate drug release. HPG-GO did not show any cytotoxicity on the MCF7 cell line in different concentrations during 72 hours' incubation. Uptake and entrance of HPG-GO into the cells were verified by determining the intracellular amount of Qu by high-performance liquid chromatography. CONCLUSION: A combination of the unique properties of GO and the biodegradable polymer polyglycerol revealed high drug-loading capacity, pH-dependent drug release, and cytocompatibility with HPG-GO, thus introducing it as a promising nanocarrier for anticancer drug delivery.

Study of orientation and penetration of LAH4 into lipid bilayer membranes: pH and composition dependence.

LAH4 is an antimicrobial peptide that is believed to possess both antibiotic and DNA delivery capabilities. It is one of a number of membrane-active peptides that show increased affinity toward anionic lipids. Herein, we have performed molecular dynamics simulations to compare LAH4 effects on anionic palmitoyl-oleoyl-phosphatidylglycerol bilayer, which approximate a prokaryotic membrane environment and zwitterionic palmitoyl-oleoyl-phosphatidylcholine bilayer, which approximate a eukaryotic membrane environment. One particular interest in this work is to study how different kinds of lipid bilayers respond to the attraction of LAH4. Remarkably, our data have shown that the depth of peptide penetration strongly depends on membrane composition and pH. At acidic pH, LAH4 has exhibited a high tendency to interact strongly with and be adsorbed on anionic membrane. We have also shown that electrostatic interactions between His11 and the phosphor atoms of bilayers should have a significant impact on the penetration of LAH4. These results provide insights into the interactions of LAH4 and lipid bilayers at the atomic level, which is useful to understand cell selectivity and mechanism of the peptide action.