Zhenhua Li

Hydrophobic Anticancer Drug Delivery by a 980 nm Laser-Driven Photothermal Vehicle for Efficient Synergistic Therapy of Cancer Cells In Vivo

A novel 980 nm laser-driven hydrophobic anticancer drug-delivery platform based on hollow CuS nanoparticles is constructed in this work. The excellent synergistic therapy combining drug treatment and photothermal ablation of cancer cells both in vitro and in vivo is demonstrated, which opens up new opportunities for biological and medical applications.

Light Controlled Reversible Inversion of Nanophosphor-Stabilized Pickering Emulsions for Biphasic Enantioselective Biocatalysis

In this work, by utilizing photochromic spiropyrans conjugated upconversion nanophosphors, we have successfully prepared NIR/visible light tuned interfacially active nanoparticles for the formulation of Pickering emulsions with reversible inversion properties. By loading a model enantioselective biocatalytic active bacteria Alcaligenes faecalis ATCC 8750 in the aqueous phase, we demonstrated for the first time that the multifunctional Pickering emulsion not only highly enhanced its catalytic performance but also relieved the substrate inhibition effect. In addition, product recovery, and biocatalysts and colloid emulsifiers recycling could be easily realized based on the inversion ability of the Pickering emulsion. Most importantly, the utilization of NIR/visible light to perform the reversible inversion without any chemical auxiliaries or temperature variation showed little damage toward the biocatalysts, which was highlighted by the high catalytic efficiency and high enantioselectivity even after 10 cycles. The NIR/visible light controlled Pickering emulsion showed promising potential as a powerful technique for biocatalysis in biphasic systems.

Luminescent Carbon Dot-Gated Nanovehicles for pH-Triggered Intracellular Controlled Release and Imaging

In this paper, the use of biocompatible carbon dots (C-Dots) as caps on the surface of mesoporous silica nanoparticles (MSPs) for the design of intelligent on-demand molecular delivery and cell imaging system is described. These C-Dots-attached MSPs exhibited low cytotoxicity toward the cells and strong luminescence both in vitro and in vivo. A further loading of anticancer drug (DOX) endowed the fluorescent material with therapeutic functions. It was found that changing the pH to mildly acidic condition at physiological temperature caused the dissociation of the C-Dots@MSPs complex and release of a large number of DOX from the nanospheres. Moreover, the DOX-loaded nanocomposites exhibited a remarkably enhanced efficiency in killing cancer cells. The endocytosis and the efficient drug release properties of the system were confirmed by luminescence microscopy. Overall, we believe that the well-designed C-Dots@MSPs nanocomposites are promising for a simultaneous bioimaging and drug delivery system, which show more potential for clinical application.

Bioresponsive Hyaluronic Acid-Capped Mesoporous Silica Nanoparticles for Targeted Drug Delivery

In this paper, we present a facile strategy to synthesize hyaluronic acid (HA) conjugated mesoporous silica nanoparticles (MSP) for targeted enzyme responsive drug delivery, in which the anchored HA polysaccharides not only act as capping agents but also as targeting ligands without the need of additional modification. The nanoconjugates possess many attractive features including chemical simplicity, high colloidal stability, good biocompatibility, cell-targeting ability, and precise cargo release, making them promising agents for biomedical applications. As a proof-of-concept demonstration, the nanoconjugates are shown to release cargoes from the interior pores of MSPs upon HA degradation in response to hyaluronidase-1 (Hyal-1). Moreover, after receptor-mediated endocytosis into cancer cells, the anchored HA was degraded into small fragments, facilitating the release of drugs to kill the cancer cells. Overall, we envision that this system might open the door to a new generation of carrier system for site-selective, controlled-release delivery of anticancer drugs.

Mesoporous silica-encapsulated gold nanoparticles as artificial enzymes for self-activated cascade catalysis

A significant challenge in chemistry is to create synthetic structures that mimic the complexity and function of natural systems. Here, a self-activated, enzyme-mimetic catalytic cascade has been realized by utilizing expanded mesoporous silica-encapsulated gold nanoparticles (EMSN-AuNPs) as both glucose oxidase- and peroxidase-like artificial enzymes. Specifically, EMSN helps the formation of a high degree of very small and well-dispersed AuNPs, which exhibit an extraordinarily stability and dual enzyme-like activities. Inspired by these unique and attractive properties, we further piece them together into a self-organized artificial cascade reaction, which is usually completed by the oxidase-peroxidase coupled enzyme system. Our finding may pave the way to use matrix as the structural component for the design and development of biomimetic catalysts and to apply enzyme mimics for realizing higher functions.

Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite

Potential bioaccumulation is one of the biggest limitations for silica nanodrug delivery systems in cancer therapy. In this study, a mesoporous silica nanoparticles/hydroxyapatite (MSNs/HAP) hybrid drug carrier, which enhanced the biodegradability of silica, was developed by a one-step method. The morphology and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2 adsorption-desorption isotherms, and XPS, and the drug loading and release behaviors were tested. TEM and ICP-OES results indicate that the degradability of the nanoparticles has been significantly improved by Ca(2+) escape from the skeleton in an acid environment. The MSNs/HAP sample exhibits a higher drug loading content of about 5 times that of MSNs. The biological experiment results show that the MSNs/HAP not only exhibits good biocompatibility and antitumor effect but also greatly reduces the side effects of free DOX. The as-synthesized hybrid nanoparticles may act as a promising drug delivery system due to their good biocompatibility, high drug loading efficiency, pH sensitivity, and excellent biodegradability.

Biomineralization inspired surface engineering of nanocarriers for pH-responsive, targeted drug delivery

Recent insight into the molecular mechanisms of natural biomineralization has enabled biomimetic synthesis of functional organic-inorganic hybrid materials under mild reaction conditions. Here, we describe a novel method to construct organic-inorganic hybrid on mesoporous silica nanoparticles by utilizing electrostatically absorbed hyaluronic acid (HA) as a reaction site for deposition of calcium phosphate (CaP) minerals. The addition of another layer of HA on the CaP surfaces not only stabilizes the nanocomposites but also confers target ability toward CD44 overexpressed cancer cells. The nanomaterials enable controlled release of loaded anticancer drugs in acidic subcellular environments after receptor mediated endocytosis. More importantly, our study demonstrated that the cancer targeting nanomaterials dramatically enhanced cellular uptake and cytotoxicity toward breast carcinoma cells. These results thus open new opportunities for biomineralization guided nanostructure assemblies with great potential for biomedical applications.

Near-Infrared Light-Triggered Drug-Delivery Vehicle for Mitochondria-Targeted Chemo-Photothermal Therapy

A novel drug-delivery vehicle for mitochondria-targeted chemo-photothermal therapy was demonstrated. A cytochrome c-specific binding aptamer was employed to make the mesoporous silica-encapsulated gold nanorods efficiently accumulate in the mitochondria of cancer cells. This nanocarrier can load various hydrophobic therapeutic agents acting on mitochondria to enhance the therapeutic efficiency and simultaneously depress the toxic side effects. In addition, near-IR treatment could induce cytochrome c release and initiation of the mitochondrial pathway of apoptosis. Importantly, this multifunctional platform could integrate targeting, light-triggered release, and chemo-photothermal therapy into one system. We hope that such a system could open the door to the fabrication of a multifunctional mitochondria-targeted drug-delivery vehicle for cancer therapy.

Noninvasive and Reversible Cell Adhesion and Detachment via Single-Wavelength Near-Infrared Laser Mediated Photoisomerization

Dynamically regulating cell-molecule interactions is fundamental to a variety of biological and biomedical applications. Herein, for the first time, by utilizing spiropyran conjugated multishell upconversion nanoparticles (UCNPs) as a new generation of single-wavelength near-infrared (NIR)-controlled photoswitch, we report a simple yet versatile strategy for controlling cell adhesion/detachment reversibly and noninvasively. Specifically, the two-way isomerization of the photoswitch was merely dependent on the excitation power density of the 980 nm laser. At high power density, the ring-opening was prominent, whereas its reverse ring-closing process occurred upon irradiation by the same laser but with the lower power density. Such transformations made the interactions between spiropyran and cell surface protein fibronectin switchable, thus leading to reversible cell adhesion and detachment. Moreover, efficient adhesion-and-detachment of cells could be realized even after 10 cycles. Most importantly, the utilization of NIR not only showed little damage toward cells, but also improved penetration depth. Our work showed promising potential for in vivo dynamically manipulating cell-molecule interactions and biological process.

Aptamer-Capped Multifunctional Mesoporous Strontium Hydroxyapatite Nanovehicle for Cancer-Cell-Responsive Drug Delivery and Imaging

A novel cancer-cells-triggered controlled-release gadolinium-doped luminescent and mesoporous strontium hydroxyapatite nanorods (designated as Gd:SrHap nanorods) system using cell-type-specific aptamers as caps has been constructed. Aptamers behave as a dual-functional molecule that acts as not only a lid but also a targeted molecular that can be used in an effective way for therapeutically special cancer cells. After incubated with cancer cells, for example, MCF-7 cells, the doxorubicin-loaded and aptamer-capped Gd:SrHap nanorods (designated as Gd:SrHap-Dox-aptamer) can be internalized into MCF-7 cells, resulting in the pore opening and drug releasing. Furthermore, the high biocompatibility and biodegradability Gd:SrHap nanorods with blue autofluorescence and paramagnetism could serve as a good contrast agent of targeting fluorescence and magnetic resonance imaging. We envision that this Gd:SrHap system could play a significant role in developing new generations of site-selective, controlled-release delivery and interactive sensory nanodevices.