Ying-Ming Zhang

Construction of a Graphene Oxide Based Noncovalent Multiple Nanosupramolecular Assembly as a Scaffold for Drug Delivery

A multiple supramolecular assembly, in which a folic acid-modified β-cyclodextrin (1) acted as a target unit, an adamantanyl porphyrin (2) acted as a linker unit, and graphene oxide acted as a carrier unit, was successfully fabricated through non-covalent interactions and comprehensively investigated by means of UV/Vis, fluorescence, and X-ray photoelectron spectroscopies, and electron microscopy. Significantly, the graphene oxide unit could associate with the anticancer drug doxorubicin through π-π interactions, and the folic acid-modified β-cyclodextrin unit could recognize the folic acid receptors in cancer cells. Owing to the cooperative contribution of these three units, the resulting multiple supramolecular assembly, after association with doxorubicin, exhibited better drug activity and much lower toxicity than free doxorubicin in vivo.

Supramolecular Architectures of β-Cyclodextrin-Modified Chitosan and Pyrene Derivatives Mediated by Carbon Nanotubes and Their DNA Condensation

Beta-cyclodextrin-modified chitosan 1 was synthesized via the Schiff base reaction between 6-O-(4-formylphenyl)-beta-cyclodextrin and chitosan (CHIT), and then the supramolecular dyad assemblies 2 and 3 were respectively fabricated from the subunit 1 through the inclusion of adamantane-modified pyrene into the beta-cyclodextrin cavity and the wrapping of a CHIT chain on multiwalled carbon nanotubes (MWCNTs). The water-soluble dyad 3 further interacted with adamantane-modified pyrene, forming a stable triad assembly 4. They were extensively characterized by NMR, thermogravimetric analysis, UV-vis, Raman spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and atomic force microscopy (AFM). Furthermore, the DNA condensation abilities of 1-4 were validated by AFM and dynamic light scattering, which indicates that the DNA-condensing capability of CHIT can be pronouncedly improved by either the pyrene grafts or the MWCNT medium. The cooperation between cationic and aromatic groups as well as the dispersion of CHIT agglomerates by MWCNTs are the key factors to enhance DNA condensation of cationic polymers.

Polysaccharide-Gold Nanocluster Supramolecular Conjugates as a Versatile Platform for the Targeted Delivery of Anticancer Drugs

Through the high affinity of the β-cyclodextrin (β-CD) cavity for adamantane moieties, novel polysaccharide-gold nanocluster supramolecular conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Due to their porous structure, the supramolecular conjugates could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), by taking advantage of the controlled association/dissociation of drug molecules from the cavities formed by the HACD skeletons and AuNPs cores as well as by harnessing the efficient targeting of cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs from the drug@HACD-AuNPs system was pH-responsive, with more efficient release occurring under a mildly acidic environment, such as that in a cancer cell. Taking the anticancer drug DOX as an example, cell viability experiments revealed that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess great potential for the targeted delivery of anticancer drugs.

Targeted Polysaccharide Nanoparticle for Adamplatin Prodrug Delivery

A series of conjugated hyaluronic acid particles (HAP), composed of a hydrophobic anticancer drug core and hydrophilic cyclodextrin/hyaluronic acid shell, were prepared through self-assembling and characterized by (1)H NMR titration, electron microscopy, zeta potential, and dynamic light-scattering experiments. The nanometer-sized HAP thus prepared was biocompatible and biodegradable and was well-recognized by the hyaluronic acid receptors overexpressed on the surface of cancer cells, which enabled us to exploit HAP as an efficient targeted delivery system for anticancer drugs. Indeed, HAP exhibited anticancer activities comparable to the commercial anticancer drug cisplatin but with lower side effects both in vitro and in vivo.

Multistimuli-Responsive Supramolecular Assembly of Cucurbituril/ Cyclodextrin Pairs with an Azobenzene-Containing Bispyridinium Guest

A linear supramolecular architecture was successfully constructed by the inclusion complexation of α-cyclodextrin with azobenzene and the host-stabilized charge-transfer interaction of naphthalene and a bispyridinium guest with cucurbit[8]uril in water, which was comprehensively characterized by (1)H NMR spectroscopy, UV/Vis absorption, fluorescence, circular dichroism spectroscopy, dynamic laser scattering, and microscopic observations. Significantly, because it benefits from the photoinduced isomerization of the azophenyl group and the chemical reduction of bispyridinium moiety with noncovalent connections, the assembly/disassembly process of this supramolecular nanostructure can be efficiently modulated by external stimuli, including temperature, UV and visible-light irradiation, and chemical redox.

Supramolecular Assembly with Multiple Preorganised π‐Electronic Cages

Kept in a cage: Complexation of phthalocyanine-grafted cyclodextrins and a sulfonated porphyrin leads to the formation of supramolecular nanowires through multivalent binding. These complexes contain multiple, preorganised π-electronic cages that efficiently capture C(60) in water.

Supramolecular Architectures by Fullerene‐Bridged Bis(permethyl‐β‐cyclodextrin)s with Porphyrins

The Hirsch-Bingel reaction of bis{4-methyl[1,2,3]triazolyl}malonic ester-bridged bis(permethyl-beta-cyclodextrin) 1 with C(60) has led to the formation of a new fullerene-bridged bis(permethyl-beta-cyclodextrin) 2, which has been comprehensively characterized by NMR spectroscopy, MALDI-MS, and elemental analysis. Taking advantage of the high affinity between 2 and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (3) or [5,10,15,20-tetrakis(4-sulfonatophenyl)porphinato]zinc(II) (4), linear supramolecular architectures with a width of about 2 nm and a length ranging from hundreds of nanometers to micron dimension were conveniently constructed and fully investigated by transmission electron microscopy (TEM), atomic force microscopy (AFM), and scanning electron microscopy (SEM). Significantly, the photoinduced electron-transfer (PET) process between porphyrin and C(60) moieties takes place within the 23 and 24 supramolecular architectures under light irradiation, leading to the highly efficient quenching of the porphyrin fluorescence. The PET process and the charge-separated state were investigated by means of fluorescence spectroscopy, fluorescence decay, cyclic voltammetry, and nanosecond transient absorption measurements.

A Supramolecular Tubular Nanoreactor

The extremely strong noncovalent complexation between the rigid host of phthalocyanine-bridged β-cyclodextrins and the amphiphilic guest carboxylated porphyrin is employed to construct a hollow tubular structure as a supramolecular nanoreactor. A representative coupling reaction occurs in the hydrophobic interlayers of the tubular walls in pure water at room temperature, leading to an enhancement of ten times higher reaction rate without any adverse effect on catalytic activity and conversion.

Phenanthroline bridged bis(β-cyclodextrin)s/adamantane-carboxylic acid supramolecular complex as an efficient fluorescence sensor to Zn2+

A water-soluble fluorescent Zn2+ sensor, 1,10-phenanthroline bridged bis(β-cyclodextrin) (1), was synthesized by “click chemistry”, and its fluorescence sensing behavior toward Zn2+ against various metal ions was investigated under physiological conditions. Significantly, 1 showed high selectivity and sensitivity toward Zn2+ with a limit of detection (LOD) down to 10−7 M. Moreover, the spectrophotometric studies demonstrated that after complexation with 1-admantanecarboxylic acid sodium salt (AdCA), the 1/AdCA complex gave much stronger binding affinity and lower LOD value toward Zn2+ through a cyclodextrin/substrate/Zn2+ triple recognition mode. The fluorescence stopped-flow experiments also indicated that the association rate of complex 1/AdCA to Zn2+ was much faster than compound 1 to the same ion. Furthermore, the fluorescence intensity of 1 and 1/AdCA was greatly enhanced after binding Zn2+ in living cells, and thus 1 and complex 1/AdCA could be considered as a biosensor for Zn2+ at the cellular level.

Reversible Molecular Switch of Acridine Red by Triarylpyridine-Modified Cyclodextrin

A novel molecular switch based on the supramolecular complex of 2,4,6-triarylpyridine modified β-cyclodextrin and acridine red was successfully constructed in aqueous solution, displaying the controlled photophysical behaviors by the effect of supramolecular positive cooperativity and fluorescence resonance energy-transfer process.