Shiyong Zhang

Tetraphenylethylene-Induced Cross-Linked Vesicles with Tunable Luminescence and Controllable Stability

Luminescence-tunable vesicles (LTVs) are becoming increasingly attractive for their potential application in optics, electronics, and biomedical technology. However, for real applications, luminous efficiency and durability are two urgent constraints to be overcome. Combining the advantages of aggregation-induced emission in luminous enhancement and cross-linking in stability, we herein fabricated tetraphenylethylene-induced cross-linked vesicles with an entrapped acceptor of RhB (TPE-CVs@RhB), which achieved a high-efficiency multicolor emission of the visible spectrum, including white, by altering the amount of entrapped acceptor. Stability tests show that the luminescence of TPE-CVs@RhB has excellent environmental tolerance toward heating, dilution, doping of organic solvent, and storage in serum. Further outstanding performance in the application of fluorescent inks suggests that the new LTVs hold high potential in industrialization. More attractively, although the TPE-CVs@RhB can tolerate various harsh conditions, their stability can actually be controlled through the cross-linker adopted. For example, the employment of dithiothreitol in the present work produces an acid-labile β-thiopropionate linker. The cellular uptake by HepG2 cells shows that the acid-labile TPE-CVs@RhB can effectively respond to the acidic environment of cancer cells and release the entrapped RhB molecules, indicative of promising applications of this new type of LTVs in bioimaging and drug delivery.

Confined Pool-Buried Water-Soluble Nanoparticles from Reverse Micelles

With the special nature of confined water pools, reverse micelles (RMs) have shown potential for a wide range of applications. However, the inherent water insolubility of RMs hinders their further application prospect especially for applications related to biology. We present herein the first successful transformation of water-insoluble RMs into water-soluble nanoparticles without changing the confined aqueous interiors by hydrolysis/aminolysis of arm-cleavable interfacial cross-linked reverse micelles formed from diester surfactant 1. The unique properties exhibited by the aqueous interiors of the resulting pool-buried water-soluble nanoparticles (PWNPs) were demonstrated both by the template synthesis of gold nanoparticles in the absence of external reductants and by the fluorescence enhancement of encapsulated thioflavin T (ThT). Importantly, the unique potential for PWNPs in biological applications was exemplified by the use of ThT@PWNPs and cell targeted ThT@PWNPs as effective optical imaging agents of living cells. This work conceptually overcomes the application bottleneck of RMs and opens an entry to a new class of functional materials.

Terminal Acetylated/Acrylated Poly(ethylene glycol) Fabricated Drug Carriers: Design, Synthesis, and Biological Evaluation

The simple acetylation or acrylation of poly(ethylene glycol) (PEG) terminus leads to the aggregation of PEG chains into spherical nanoparticles in water at room temperature and very low concentrations. The experiment results suggest that this aggregation happens by the variation of the local conformation of the O-CH2-CH2-O segments of PEG chains caused by the introduced acyl group, which disturbs the originally strict hydrogen bond mode between the O-CH2-CH2-O groups and the water molecules. The simple modified PEG nanoparticles are excellent carriers for drug delivery. As examples, the cross-linkable 1d-based drug delivery systems, cPEG@SN-38 and targeted cPEG@SN-38, are successfully established by their high drug loading content (18 wt %/wt) and enhanced anticancer efficacy both in vitro and in vivo while obviating the inherent toxicity of the employed chemotherapeutics. This strategy that revolves around the simple modification of the generally regarded as safe (GRAS) modules to fabricate drug carriers represents a new direction for the drug delivery systems with clinical potential.

Latent Naphthalimide Bearing Water-Soluble Nanoprobes with Catechol–Fe(III) Cores for in Vivo Fluorescence Imaging of Intracellular Thiols

Here, a novel latent naphthalimide bearing water-soluble nanoprobes with catechol-Fe(III) cores (Fe@LNNPs) was designed, synthesized, and evaluated for in vivo fluorescence imaging of intracellular thiols, as various diseases are associated with overexpression of cellular biothiols. The Fe@LNNPs are mainly composed of three components. The inner part constitutes pyrocatechol groups, which can coordinate with Fe(III) to form a cross-linked core for improving the stability in the complex biological environment. The naphthalimide group is linked by disulfide with the core to quench the probe fluorescence. The outer part is designed to be a hydrophilic glycol corona for prolonging blood circulation. Also, a biotin group can be easily introduced into the nanoprobe for actively targeting the HepG2 cells. The fluorescence spectra reveals that the Fe@LNNPs can be reduced explicitly by glutathione to trigger the fluorescence emission. Confocal microscopic imagings and animal experiments manifest that the Fe@LNNPs, especially with biotin groups, have much better fluorescence signal imaging compared to the reported small-molecule probe 1 both in vitro and in vivo (up to 24 h). The Fe@LNNPs thus feature great advantages such as specificity, stability, biocompatibility, and long retention time for thiol-recognition imaging and hold potential applications in clinical cancer diagnosis.

Co-solvent polarity controlled self-assembly of tetraphenylethylene-buried amphiphile for size-regulated tumor accumulation

Abstract We report that the co-solvent polarity can precisely control the TPE-buried amphiphile 1 to self-assemble into nanoparticles (NPs) in water with size range from ∼21–32u2009nm to 55–68u2009nm to 95–106u2009nm. Excepted for size, these TPE-buried amphiphile fabricated NPs hold identical physical properties such as spherical shape, surface charge, and luminescent properties, and moreover, after covalent capture of the acrylate hydrophilic heads, the resulting cross-linked NPs (cNPs I–III) own excellent in vivo stability, which thus would be an ideal platform for investigating the size effects on tumor accumulation and penetration.

Antibacterial coordination polymer hydrogels composed of silver(I)-PEGylated bisimidazolylbenzyl alcohol

Herein, antibacterial coordination polymer hydrogels were conveniently fabricated in water via coordination between silver nitrate and PEGylated bisimidazolylbenzyl alcohol (1a–c). These coordination polymer hydrogels exhibit much better antibacterial activity than silver nitrate against both Gram-negative and Gram-positive pathogens including multidrug-resistant pathogens. The coordination polymer Ag/1c with a long PEG chain (PEG1000) was demonstrated to be the most effective antibacterial material, and its minimum inhibition concentrations (MICs) could be as low as 15.2 times for common Staphylococcus aureus and 4.8 times for methicillin-resistant Staphylococcus aureus over that of silver nitrate. With improved antibacterial performance, easy preparation method, improved stability, sustained releasability, outstanding ductility and low cytotoxicity, the as-prepared coordination polymer hydrogels should find various potential applications such as in clinical burn and wound dressings, biofilms, bioadhesives, and coatings of biomedical materials.

DOTA Functionalized Cross-Linked Small-Molecule Micelles for Theranostics Combining Magnetic Resonance Imaging and Chemotherapy

Herein, a new theranostic nanoplatform was built by introducing DOTA on the surface of the cross-linked small molecular micelles. This nanoplatform consisted of three parts: (1) Hydrophobic alkyl chain functioned with alkenes as cross-linkable part to ensure the robust stability in vivo; (2) Hydrophilic DOTA for not only gadolinium ions complexion as MR imaging contrast agents but also platinum ions complexion as drug carriers; (3) Cisplatin as antitumor drug and MR imaging amplifier simultaneously. The metal loading content of the resulting Pt/Gd@DOTA-CSMs was up to 12 and 14 wt % for Gd(III) and Pt(II), respectively. The longitudinal relaxation rate of Gd@DOTA-CSMs (8.46 mM-1 s-1) was 2.6 times than that of the clinical Gd-DTPA (3.23 mM-1 s-1). When cisplatin was involved, not only great antitumor efficiency was achieved, but higher longitudinal relaxation rate of Pt/Gd@DOTA-CSMs (11.17 mM-1 s-1) was carried out due to the extension of rotational correlation time. The experiments of Balb/c mice bearing 4T1 xenograft indicated that Pt/Gd@DOTA-CSMs had better antitumor activity, lower side effect than clinically used cisplatin, and greater MR imaging than Gd-DTPA. All the results proved that the nanoplatform of DOTA-CSMs held remarkable potential in the field of therapeutics.