Meili Yin

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.

The use of multifunctional magnetic mesoporous core/shell heteronanostructures in a biomolecule separation system

A multifunctional magnetic mesoporous core/shell heteronanostructure (designated as Fe(3)O(4)@NiSiO(3)) has been designed and constructed that combined the capacity of effective protein purification from protein mixture and selective low molecule weight (MW) biomolecule enrichment. The nanoparticle is composed by magnetite nanoparticle with immobilized metal ion surface and solid porous shell which presents a number of important features, such as controllable shell thickness, uniform pore size and excellent magnetism. By taking advantages of the high affinity of Ni(2+) on the shell surface toward His-tagged proteins and the fast response toward an assistant magnet, the heteronanoparticles can be applied to selectively bind to and magnetically separate of His-tagged proteins from a cell lysate of E. coli. Additionally, owing to the homogeneous 3D mesopores on the nickel silicate shell, the heteronanoparticles can selectively capture low MW biomolecules from complex mixture. Significantly, it is expected that this approach can be extended to other biomolecule separation and enrichment systems by changing the immobilized surface and the pore size.

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.

DNA‐mediated Construction of Hollow Upconversion Nanoparticles for Protein Harvesting and Near‐Infrared Light Triggered Release

A simple DNA-mediated solvothermal method has been developed for the construction of well-defined hollow UNPs that can be used for a new paradigm to realize NIR light-controlled non-invasive protein release. In vitro studies show that the UNPs are capable of the transportation of enzyme into living cells. Intracellular NIR triggers the release of enzymes with high spatial and temporal precision and the released enzyme also retains its biological activity.

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.

Reduced Graphene Oxide Upconversion Nanoparticle Hybrid for Electrochemiluminescent Sensing of a Prognostic Indicator in Early-Stage Cancer

Upconversion nanoparticles (UCNPs) have been proposed as a promising new class of biological luminescent labels because of their weak auto-fluorescence background, strong penetration ability under near-infrared (NIR) radiation, resistance to photobleaching, and low toxicity. Although UCNPs hold great promise in nanotechnology and nanomedicine, their applications in ECL fields still remain unexplored. Herein, a label-free, ultra-sensitive and selective electrochemiluminescence (ECL) assay is developed for detection of cyclin A2 by using highly efficient ECL graphene-upconversion hybrid. Being an important member of the cyclin family, cyclin A2 is involved in the initiation of DNA replication, transcription and cell cycle reg-ulation through the association of cyclin-dependent kinases (CDK). Cyclin A2 is a prognostic indicator in early-stage cancers and a target for treatment of different types of cancers. However, the expression level of cyclin A2 is quite low, direct detection of cyclin A2 in crude cancer cell extracts is challenging and important for both clinical diagnosis of cancer in the early stage and the treatment. By chemically grafting cyclin A2 detection specific probe, a PEGlyted hexapeptide, to graphene-upconversion hybrid, the constructed ECL biosensor displays a superior performance for cyclin A2 , which can not only detect cyclin A2 directly in cancer cell extracts, but also discriminate between normal cells and cancer cells. More importantly, the ECL biosensor has different responses between clinical used anticancer drug-treated and non-treated cancer cells, which demonstrates that the sensor can be potentially used for drug screening, and for evaluation of therapeutic treatments in early-stage cancers.

Photosensitizer-incorporated G-quadruplex DNA-functionalized magnetofluorescent nanoparticles for targeted magnetic resonance/fluorescence multimodal imaging and subsequent photodynamic therapy of cancer

A smart heteronanostructure has been constructed for targeted photodynamic therapy and magnetic fluorescent imaging of cancer cells using photosensitizer-incorporated G-quadruplex DNA functionalized magnetic nanoparticles.

Upconverting Nanoparticles with a Mesoporous TiO2 Shell for Near-Infrared-Triggered Drug Delivery and Synergistic Targeted Cancer Therapy

Malignant tumors remain a major health burden throughout the world and effective therapeutic strategies are urgently needed. Herein, we report the synthesis of upconverting nanoparticles with a mesoporous TiO2 (mTiO2) shell for near-infrared (NIR)-triggered drug delivery and synergistic targeted cancer therapy. The NaGdF4:Yb,Tm could convert NIR light to UV light, which activated the mTiO2 to produce reactive oxygen species for photodynamic therapy (PDT). Due to the large surface area and porous structure, the mTiO2 shell endowed the nanoplatform with another functionality of anticancer drug loading for chemotherapy. The hyaluronic acid modified on the surface not only promised controlled drug release but also conferred targeted ability of the system toward cluster determinant 44 overexpressed cancer cells. More importantly, cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of breast carcinoma cells compared with that of single chemotherapy or PDT.

DNA-mediated biomineralization of rare-earth nanoparticles for simultaneous imaging and stimuli-responsive drug delivery

A DNA-guided method for surface engineering of NaGdF4:Ce/Tb hybrid nanoparticle has been proposed. In this study, the DNA molecules that retained after one-pot NaGdF4:Ce/Tb synthesis is directly utilized as biotemplate for CaP heterogeneous nucleation, thus the dual-purpose function of DNA is realized in the current study which could afford a new type of pH-responsive theranostic platform to enhance the therapeutic efficiency while minimizing side effects. The introduction of another layer of aptamer molecules on CaP facilitated cellular uptake of the resulting nanocomposite into specific target cells via receptor-mediated endocytosis. After been taken by the target tumor cells, the NaGdF4:Ce/Tb@CaP was found to be mostly accumulated in lysosome, which facilitated the dissolving of CaP coatings as non-toxic ions to initiate drug release and efficient cancer cell destruction. We envision that the hybrid nanocarrier may serve as practical and multifunctional probe for cancer therapy and the presented synthesis approach here may also benefit the preparation of many other types of multifunctional inorganic-biomolecular hybrid nanostructures based on the DNA nanotechnology.

Combination Delivery of Antigens and CpG by Lanthanides-Based Core-Shell Nanoparticles for Enhanced Immune Response and Dual-Mode Imaging

Europium-doped GdPO4 hollow spheres/polymer core-shell nanoparticles are functionalized with ovalbumin (OVA) as a model antigen and an oligonucleotide (CpG) that stimulates the immune response. These functionalized core-shell nanoparticles are used as vaccines, where they enable efficient delivery of an antigen to target sites, tracking of the vaccines using non-invasive clinical imaging technology.