Soo Zeng Fiona Phua

Theranostic Prodrug Vesicles for Imaging Guided Codelivery of Camptothecin and siRNA in Synergetic Cancer Therapy

The construction of prodrugs has been a popular strategy to overcome the limitations of chemotherapeutic drugs. However, complicated synthesis procedures and laborious purification steps make the fabrication of amphiphilic prodrugs rather difficult. By harnessing the concept of host-guest interaction, we designed and prepared a supra-amphiphile consisting of a dendritic cyclodextrin host and an adamantane/naphthalimide-modified camptothecin guest through glutathione-responsive disulfide linkage. This host-guest complex could self-assemble in aqueous solution to give nanosized vesicles. When the disulfide bond in adamantane/naphthalimide-modified camptothecin was cleaved by glutathione, the fluorescence of the freed adamantane/naphthalimide unit showed a significant red shift with enhanced intensity. Such glutathione-responsive fluorescence change allows for intracellular imaging and simultaneous monitoring of drug release in real time. On account of abundant positively charged amine groups on the supramolecular vesicle surface, siRNA (siPlK1) could be efficiently loaded on the vesicle. The gel retardation and fluorescence experiments proved that the siPlK1 was successfully bonded to the supramolecular vesicle. The vesicle with dendritic cyclodextrin ring exhibited negligible cytotoxicity even at high concentrations, avoiding the shortcoming of cytotoxicity from commonly used gene vectors. In vitro studies demonstrated that the loaded siRNA was transported into cancer cells to improve cancer therapeutic efficacy. Thus, we developed a prodrug-based supramolecular amphiphile via the host-guest interaction with better therapeutic performance than free camptothecin. The assembled system was utilized as a drug/gene vector to achieve combinational gene therapy and chemotherapy with a synergistic effect, providing an alternative strategy to deliver both prodrug and therapeutic gene.

A transferrin-conjugated hollow nanoplatform for redox-controlled and targeted chemotherapy of tumor with reduced inflammatory reactions

Purpose: In this study, we report the design, development and evaluation of a hollow drug delivery nanoplatform for cancer therapy in vitro and in vivo. This composite nanosystem was prepared by modifying hollow mesoporous silica nanoparticles (HMSNs) with transferrin (Tf) targeting moieties via redox-liable linkage, and was capable of delivering therapeutic cargos (doxorubicin) specifically to the tumor site and subsequently releasing them in an on-demand manner. Moreover, the Tf corona could simultaneously reduce the inflammatory response after intravenous administration in vivo. Methods: Nanostructural morphology of the drug delivery system was observed by scanning electron microscope and transmission electron microscope. The preparation process was monitored primarily using Fourier-transform infrared spectroscopy, dynamic light scattering, nitrogen adsorption/desorption isotherm, and thermogravimetric analysis. The release profile in solution was monitored by fluorescence spectroscopy. In vitro drug delivery efficacy was evaluated on MDA-MB-231 breast cancer cell line using confocal laser scanning microscopy, MTT assay and flow cytometry. In vitro inflammatory response was evaluated on RAW264.7 macrophage cells. In vivo therapeutic experiments were carried out using in situ mouse breast cancer models. Results: The experimental results evidently demonstrate that the developed nanocarrier could effectively deliver anticancer drugs to the tumor site in a targeted manner and release them in response to the elevated glutathione level inside tumor cells, resulting in improved anticancer efficacy both in vitro and in vivo. Moreover, the Tf conjugation significantly ameliorated the inflammatory reaction triggered by the administration of the nanocarrier. Conclusions: This manuscript demonstrated that the Tf-conjugated HMSNs could enhance the delivery efficiency of anticancer drugs, while simultaneously alleviating the adverse side effects. The current study presents a promising integrated delivery system toward effective and safe cancer treatment.

Ultralong room temperature phosphorescence from amorphous organic materials toward confidential information encryption and decryption

Ultralong room temperature phosphorescence is achieved from amorphous organic materials toward information encryption. Ultralong room temperature phosphorescence (URTP) emitted from pure amorphous organic molecules is very rare. Although a few crystalline organic molecules could realize URTP with long lifetimes (>100 ms), practical applications of these crystalline organic phosphors are still challenging because the formation and maintenance of high-quality crystals are very difficult and complicated. Herein, we present a rational design for minimizing the vibrational dissipation of pure amorphous organic molecules to achieve URTP. By using this strategy, a series of URTP films with long lifetimes and high phosphorescent quantum yields (up to 0.75 s and 11.23%, respectively) were obtained from amorphous organic phosphors without visible fluorescence and phosphorescence under ambient conditions. On the basis of the unique features of URTP films, a new green screen printing technology without using any ink was developed toward confidential information encryption and decryption. This work presents a breakthrough strategy in applying amorphous organic materials for URTP.

Helicity Inversion of Supramolecular Hydrogels Induced by Achiral Substituents

Probing the supramolecular chirality of assemblies and controlling their handedness are closely related to the origin of chirality at the supramolecular level and the development of smart materials with desired handedness. However, it remains unclear how achiral residues covalently bonded to chiral amino acids can function in the chirality inversion of supramolecular assemblies. Herein, we report macroscopic chirality and dynamic manipulation of chiroptical activity of hydrogels self-assembled from phenylalanine derivatives, together with the inversion of their handedness achieved solely by exchanging achiral substituents between oligo(ethylene glycol) and carboxylic acid groups. This helicity inversion is mainly induced by distinct stacking mode of the self-assembled building blocks, as collectively confirmed by scanning electron microscopy, circular dichroism, crystallography, and molecular dynamics calculations. Through this straightforward approach, we were able to invert the handedness of helical assemblies by merely exchanging achiral substituents at the terminal of chiral gelators. This work not only presents a feasible strategy to achieve the handedness inversion of helical nanostructures for better understanding of chiral self-assembly process in supramolecular chemistry but also facilities the development of smart materials with controllable handedness in materials science.

Cyclometalated Iridium(III)-Complex-Based Micelles for Glutathione-Responsive Targeted Chemotherapy and Photodynamic Therapy

The integration of chemotherapy and photodynamic therapy (PDT) in a single delivery system is highly desirable for enhancing anticancer therapeutic efficacy. Herein, two cyclometalated Ir(III) complex-constructed micelles FIr-1 and FIr-2 were demonstrated for glutathione (GSH) activated targeted chemotherapy and PDT. The cyclometalated Ir(III) complexes were prepared by conjugating phosphorescent Ir(III) compounds with chemotherapeutic drug camptothecin (CPT) through GSH responsive disulfide bond linkages, and the Ir(III) complexes were then assembled with amphiphilic surfactant pluronic F127 via noncovalent encapsulation to afford micelles. The surfaces of the micelles were further decorated with folic acid as a targeting group. The micelles showed intense fluorescence that renders them with excellent real-time imaging capability. The release of free anticancer drug CPT from the micelles was realized through GSH-activated disulfide bond cleavage in tumor cells. In addition, the micelles were capable of generating singlet oxygen used for PDT upon visible light irradiation. On account of having folic acid targeting ligand, the micelles displayed greater cellular accumulation in folate receptor (FR) overexpressed HeLa cells than FR low-expressed MCF-7 cells, leading to selective cancer cell killing effect. As compared with solo therapeutic systems, the micelles with targeted combinational chemotherapy and PDT presented superior potency and efficacy in killing tumor cells at a low dosage. On the basis of these findings, the multifunctional micelles could serve as a versatile theranostic nanoplatform for cancer cell targeted imaging and combinational therapy.

Water‐Binding‐Mediated Gelation/Crystallization and Thermosensitive Superchirality

Determination of molecular structural parameters of hydrophobic cholesterol-naphthalimide conjugates for water binding capabilities as well as their moisture-sensitive supramolecular self-assembly were revealed. Water binding was a key factor in leading trace water-induced crystallization against gelation in apolar solvent. Ordered water molecules entrapped in self-assembly arrays revealed by crystal structures behave as hydrogen-bonding linkers to facilitate three-dimensional growth into crystals rather than one-dimensional gel nanofibers. Water binding was also reflected on the supramolecular chirality inversion of vesicle self-assembly in aqueous media via heating-induced dehydration. Structural parameters that favor water binding were evaluated in detail, which could help rationally design organic building units for advancing soft materials, crystal engineering, and chiral recognition.

Programmable Multicomponent Self-Assembly Based on Aromatic Amino Acids

Construction of integrated self-assembly with ordered structures from two or more organic building blocks is currently a challenge, since it suffers from intrinsic systematic complexity and diverse competitive pathways. Here, it is reported that aromatic amino acid building units can be incorporated into two- or three-component coassembly driven primarily by hydrogen bonding interactions without the assistance of metal-ligand and macrocycle-based host-guest interactions. The key strategy is to employ a C3 -symmetric molecule with alternative hydrogen bonding donor/acceptor sites that are able to bind either carboxylic acid or pyridine appended building units. Aromatic amino acids, C3 -symmetric compound, and bipyridine unit constitute a unique ternary mutual binding system, where three coassembly pathways including two pairwise formations and one ternary combination are unveiled, giving rise to two- and three-component self-assemblies with ordered structures, respectively. The pathway complexity lies in the structural parameter of aromatic amino acids, which can be programmable by controlling substituents at the α-position of amino acids.