Weihua Zhuang

In situ synthesis of multidentate PEGylated chitosan modified gold nanoparticles with good stability and biocompatibility

To realize desirable functions in the rather complex biological systems, a suitable surface coating is desirable for gold nanoparticles, which plays an important role in their colloidal stability and biocompatibility. In this work, a novel multidentate PEGylated chitosan derivative was synthesized by conjugating PEG and dithiolane lipoic acid (LA) to the chitosan backbone. Under reduction conditions, gold nanoparticles (AuNPs) could be in situ formed by the electrostatic interaction between amino groups of the chitosan derivative and gold chloride ions (AuCl4−), with their surface covalently coated by the multidentate PEGylated chitosan via the disulfide bond from LA. After the surface modification, such AuNPs exhibited remarkable colloidal stabilities under extreme conditions, including high salt conditions and complex biological media containing serum. Moreover, the multidentate PEGylated chitosan also provided AuNPs with good biocompatibility and low cytotoxicity, resistance of protein adsorption and anti-phagocytosis by RAW 264.7 cells. This kind of AuNP was expected to be a promising platform for applications in nanomedicine.

pH-sensitive doxorubicin-conjugated prodrug micelles with charge-conversion for cancer therapy

Intelligent drug delivery systems with prolonged circulation time, reduced drug leakage in blood, target site-triggered drug release and endosomal escape are attractive and ideal for malignant tumor therapy. Herein, doxorubicin (DOX)-conjugated smart polymeric micelles based on 4-carboxy benzaldehyde-grafted poly (L-lysine)-block-poly (methacryloyloxyethyl phosphorylcholine) (PLL(CB/DOX)-b-PMPC) copolymer are prepared. DOX and electronegative 4-carboxy benzaldehyde are conjugated to the PLL block via an imine linkage and as a result, the drug loaded micelles exhibited the pH-triggered charge-conversion property and accelerated drug release at tumor pH. In vitro cytotoxicity studies of these DOX-loaded micelles exhibited great tumor inhibition against HeLa and 4T1 cells. Moreover, in mice models of breast cancer, these DOX-loaded micelles showed better anti-tumor efficacy and less organ toxicity than free drug. In summary, these polymeric micelles could be applied as potential nanocarriers for cancer therapy. STATEMENT OF SIGNIFICANCE As a typical anti-cancer drug, Doxorubicin (DOX) exhibited remarkable tumor inhibition but was limited by its low drug utilization and strong toxicity to organs. To overcome these challenges, we developed a DOX-conjugated polymeric micelle as a nano drug carrier which was endowed with pH-sensitivity and charge-conversion function. The structure of micelles would quickly disintegrate with surface charge-conversion in acidic environment, which would contribute to the endosomal escape and accelerated drug release. These DOX-conjugated micelles would provide a promising platform for the efficient DOX delivery and better anti-cancer efficiency.

Preparation of organic mechanochromic fluorophores with simple structures and promising mechanochromic luminescence properties

Organic mechanochromic fluorescent materials have attracted increasing interest over the last few years. However, organic mechanochromic fluorophores reported so far usually have complicated structures and require multi-step synthesis. In this paper, a simple method to design and synthesize organic mechanochromic fluorophores with simple structures and promising mechanochromic luminescence properties is reported. Based on this method, a broad range of pyrene-based phosphonium materials with promising mechanochromic luminescence have been developed. Among all pyrene-based mechanochromic materials reported so far, tributyl(pyren-1-ylmethyl)phosphonium fluorophore 1·PF6 reported in this paper is the smallest pyrene-based mechanochromic fluorophore with the longest emission wavelength shift. The method reported in this study has shown great potential for the rapid construction of mechanochromic materials and opened a new avenue to develop novel mechanochromic materials.

A fully absorbable biomimetic polymeric micelle loaded with cisplatin as drug carrier for cancer therapy

Abstract cis-dichlorodiammineplatinum(II) (CDDP)-loaded polymeric micelles for cancer therapy have been developed to reduce the serious side effects of cisplatin CDDP. Herein, polymeric micelles incorporated with cisplatin are prepared based on the complexation between CDDP and hydrophilic poly (L-glutamic acid)-b-poly (2-methacryloyloxyethyl phosphorylcholine) (PLG-b-PMPC) diblock copolymers. These CDDP-loaded micelles possess an average size of 91 nm with narrow distribution, providing remarkable stability in media containing proteins. The release of CDDP from the micelles is faster at pH 5.0 and pH 6.0 than that at pH 7.4 and in a sustained manner without initial burst release. In addition, there is almost no difference in cellular uptake between these CDDP-loaded micelles and free CDDP. Moreover, in vitro cytotoxicity test shows they possess high efficacy to kill 4T1 cells as compared with free drug. Thus, PLG-b-PMPC copolymer might be a promising carrier for CDDP incorporating in cancer therapy.

High contrast stimuli-responsive luminescence switching of pyrene-1-carboxylic esters triggered by a crystal-to-crystal transition

Unexpected high contrast mechanochromic, thermochromic and vaporchromic luminescence has been achieved through a simple introduction of an ester group to a pyrene skeleton and a series of stimuli-responsive materials based on pyrene-1-carboxylic esters were efficiently developed. The mechanistic investigation of stimuli-responsive luminescence indicates that the emission change might be ascribed to a reversible crystal-to-crystal transition. Furthermore, the electron-withdrawing effect of the ester groups to suppress the π–π interaction of the pyrene rings might be the key factor to trigger the promising stimuli-responsive luminescence.

Cation–anion interaction directed dual-mode switchable mechanochromic luminescence

In the past few years, organic mechanochromic materials have attracted more and more attention and a number of organic mechanochromic materials have been reported. However, only a single mode for switching of mechanochromic luminescence, either red-shift or blue-shift of the luminescence, can be observed for all the reported mechanochromic materials. Herein, based on a single tributyl(perylen-3-ylmethyl)phosphonium (TPMP) fluorophore, dramatic dual-mode switchable mechanochromic luminescence triggered by tunable cation–anion interactions has been reported for the first time. The trend of mechanochromic luminescence changes gradually from a red-shift to a blue-shift along with the strength order of the cation–anion interaction: Br− > BF4− > PF6− > NTf2−. A reversible transition of a crystalline state to an amorphous phase might be involved in the mechanochromic luminescence of TPMP·X (X = counteranion) with different counteranions.

A biomimetic and pH-sensitive polymeric micelle as carrier for paclitaxel delivery

Abstract As nano-scale drug delivery systems, smart micelles that are sensitive to specific biological environment and allowed for target site-triggered drug release by reversible stabilization of micelle structure are attractive. In this work, a biocompatible and pH-sensitive copolymer is synthesized through bridging poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC) block and poly (D, L-lactide) (PLA) block by a benzoyl imine linkage (Blink). Biomimetic micelles with excellent biocompatibility based on such PLA-Blink-PMPC copolymer are prepared as carriers for paclitaxel (PTX) delivery. Due to the rapid breakage of the benzoyl imine linkage under acidic condition, the micelle structure is disrupted with accelerated PTX release. Such pH-sensitive triggered drug release behavior in synchronization with acidic conditions at tumor site is helpful for improving the utilization of drug and facilitating antitumor efficacy. These micelles can be used as promising drug delivery systems due to their biocompatible and smart properties.

Cation–anion interaction-directed formation of functional vesicles and their biological application for nucleus-specific imaging

A strategy for construction of counterion-induced vesicles in aqueous media has been described using imidazolium salts with multiple imidazolium moieties and alkyl carboxylate counteranions. The spontaneous formation of vesicles can be achieved by the simple selection of the counteranion to satisfy the requirement of the packing parameter for vesicle formation. Functional fluorescent vesicles can also be formed by the introduction of an aggregation-induced emission (AIE) fluorophore, tetraphenylethene (TPE), as the core of the imidazolium salt TPEI-C8, which also exhibits highly specific nucleus imaging in living cells. Considering the distinct AIE characteristic of TPEI-C8, the aggregation-induced strong fluorescence emission of TPEI-C8 in the cell nucleus may be the main reason for the specific fluorescence images of the cell nucleus. The strategy for the construction of functional vesicles reported in this study has shown great potential for the construction of other functional vesicles.

Micelles prepared from poly(N-isopropylacrylamide-co-tetraphenylethene acrylate)-b-poly [oligo(ethylene glycol) methacrylate] double hydrophilic block copolymer as hydrophilic drug carrier

Self-assembled micelles obtained from a double hydrophilic block copolymer (DHBC) based on poly(N-isopropylacrylamide) (PNIPAAm) are a facile and green strategy compared to the conventional solvent exchange method. However, hydrophobic drug encapsulation in micelles from PNIPAAm-based DHBC has relatively low drug loading (DL) and encapsulation efficiency (EE). Intermolecular and intramolecular hydrogen bondings of PNIPAAm chains are formed to exclude hydrophobic drugs. Nevertheless, hydrogen bonding can be used for hydrophilic drug delivery. Therefore, we report micelles prepared from a poly(N-isopropylacrylamide-co-tetraphenylethene acrylate)-b-poly[oligo(ethylene glycol) methacrylate] [P(NIPAAm-co-TPE)-b-POEGMA] double hydrophilic block copolymer as a hydrophilic drug (thymopentin, TP5) carrier. The FTIR results confirm hydrogen bond formation between PNIPAAm chain and TP5. Micelles are obtained by simply increasing the temperature above the critical micelle temperature (CMT). The self-assembly behaviour of polymeric micelles is investigated by DLS, TEM and aggregation-induced emission (AIE) phenomenon. Cytotoxicity results indicate that the micelles are biocompatible. The in vitro prolonged drug release (from 6 min to several hours) and in vivo immunity enhancement indicate that the micelles formed by P(NIPAAm-co-TPE)-b-POEGMA DHBC are promising candidates as hydrophilic drug carriers, where hydrogen bonding is formed between PNIPAAm and drug.

Multifunctional coatings that mimic the endothelium: surface bound active heparin nanoparticles with in situ generation of nitric oxide from nitrosothiols

Multifunctional coatings that mimic the endothelial function in terms of nitric oxide generation and membrane-bound active heparin species are prepared via the immobilization of cystamine-modified heparin/polyethyleneimine (Hep-Cys/PEI) nanoparticles. Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) were conducted to confirm the coating formation. Functions of active heparin release and nitric oxide (NO) generation are obtained on the material surface after the immobilization of Hep-Cys/PEI nanoparticles. Moreover, a nanoparticle-immobilized coating is sufficiently flexible to resist the deformation of a 316L SS stent without any destruction. With the introduction of heparin, the antithrombin III (AT-III) binding ability was significantly enhanced with prolonged APTT time. Besides, a Hep-Cys/PEI nanoparticle immobilized coating surface not only significantly suppressed the platelet adhesion and activation, but also promoted EC proliferation and inhibited SMC proliferation. Besides, a milder tissue response was observed on the NP immobilized surface. With the synergistic effect of heparin and nitric oxide generating moieties, such multifunctional coatings presented potential for the modification of vascular materials.