Zhang Xianzheng

Template-module assembly to prepare low-molecular-weight gene transport system with enhanced transmembrane capability

Based on specific host-guest interactions between amine-modified β-cyclodextrin (CD-TAEA) and functional adamantane (AD) derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assemblies for gene transport. This strategy offers great flexibility in terms of the introduction of mono- or multi-functionality by the inclusion of one or more adamantane-based modules with the desired functionalities. As proof of concept, phenylboronic acid (PB) containing adamantane (PB-AD) was used as a model module in the hope of offering enhanced cytosolic delivery in consideration of the special affinity of PB groups with cell membranes. The physicochemical properties of the complexes formed with plasmid DNA, such as particle size, zeta potential and morphology were investigated. Confocal laser scanning microscopy and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the considerably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CD-TAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CD-TAEA displayed much lower cytotoxicity than PEI25K in both 293T and HeLa cell lines. The encouraging results suggest that CD-TAEA can be developed as a powerful template capable of readily accommodating various AD-based modules giving versatile functionalities for improved transfection.

The design and application of functionalized mesoporous silica nanocarrier

With the rapid development of nanotechnology, nanomaterials with unique physical and chemical characteristics, have offered tremendous potential for biomedical application. Among them, mesoporous silica nanoparticles (MSNs), a class of well-established nanoplatforms with different structures and compositions, have been widely used to develop drug delivery systems owing to their unique physical-chemical properties, such as tunable particle/pore size, high surface area and pore volume, easy surface modification, remarkable stability and biocompatibility, and high drug loading efficiency. Moreover, MSN-based nanocarriers with “zero premature release” property have proven to be excellent devices for drug delivery. A variety of fluorescent dyes and pharmaceutical drugs were encapsulated in MSNs for controlled release. In addition, numerous efforts have been made to develop smart nanovalves on the surface of MSN to provide on-command release of drug in response to different stimuli, including light, enzymes, pH, redox, temperature, and competitive molecules. Furthermore, the outer surface of MSN can be modified with various functional groups, that play critical roles (stealth or targeting) in overcoming the multistage barriers found in the drug delivery process. Fabrication of MSN-based, multifunctional, stimuli-responsive drug delivery systems can effectively encapsulate anticancer drugs and can maintain “zero premature release” before reaching the diseased site. Once they arrive at the tumor site with the aid of targeting groups, the nanodevice can be activated by a specific stimulus to release the drug. The delivery of anticancer drugs to a specific target site can alleviate toxic side effects and improve the therapeutic index of drugs; thus, achieving significantly enhanced anticancer efficiency. Herein, we reviewed various strategies for the design of stimuli-responsive, MSN-based drug delivery systems, and multifunctional MSN for targeted cancer therapy.

Molecular self-assembly of peptide

Arising from the abundant protein self-assemblies existing in nature, recently, the self-assembly of peptides has been a research focus. Through rational designing the molecular structures of peptides and altering the external environment, peptides can spontaneously or induced self-assemble into specific-shape aggregates via noncovalent forces, such as hydrogen bonding, hydrophobic and π-stacking interactions etc. Due to well biocompatibility and controlled degradation, functional materials constructed from the self-assembly of peptides present a great potential in many biomedical fields. This review explores the research progress of the self-assembly of peptides in the past two decades. The structure motifs used in the self-assembly of peptide, self-assembly mechanisms, morphologies as well as the biomedical applications of the self-assembled peptides are also reviewed in detail.