Chuan Zhang

Graphene oxide doped conducting polymer nanocomposite film for electrode-tissue interface

One of the most significant components for implantable bioelectronic devices is the interface between the microelectrodes and the tissue or cells for disease diagnosis or treatment. To make the devices work efficiently and safely in vivo, the electrode-tissue interface should not only be confined in micro scale, but also possesses excellent electrochemical characteristic, stability and biocompatibility. Considering the enhancement of many composite materials by combining graphene oxide (GO) for its multiple advantages, we dope graphene oxide into poly(3,4-ethylenedioxythiophene) (PEDOT) forming a composite film by electrochemical deposition for electrode site modification. As a consequence, not only the enlargement of efficient surface area, but also the development of impedance, charge storage capacity and charge injection limit contribute to the excellent electrochemical performance. Furthermore, the stability and biocompatibility are confirmed by numerously repeated usage test and cell proliferation and attachment examination, respectively. As electrode-tissue interface, this biomaterial opens a new gate for tissue engineering and implantable electrophysiological devices.

Effects of Large Blood Vessel Locations during High Intensity Focused Ultrasound Therapy for Hepatic Tumors: a finite element study

High-intensity focused ultrasound (HIFU) has become a viable alternative for treatment of primary and metastatic liver tumors. We evaluated the effects of presence of a large blood vessel and its distance to the tumor on lesion size during HIFU heating. A finite element method (FEM) was used to obtain the temperature distribution for a transfer equation based on large blood vessels convection effect. In 3-D FEM simulation, a 4-mm diameter, 10-mm height cylindrical tumor tissue was heated by different heating schemes with a large blood vessel (10-mm diameter) located at different positions nearby. The distance between the vessel and the tumor tissue varied from 1 mm to 3 mm. For HIFU therapy, the large blood vessel of different locations do not have significant effect on temperature distribution and thermal dose profile, when the heating duration is short (~2s) or the distance of the large blood vessel from the tumor is larger than 2 mm. The domain of thermal lesion can effectively cover the desired therapeutic region with short ultrasound exposure duration (~2s)

A Molecular Recognition Approach To Synthesize Nucleoside Analogue Based Multifunctional Nanoparticles for Targeted Cancer Therapy

Tumor-targeted drug delivery with simultaneous cancer imaging is highly desirable for personalized medicine. Herein, we report a supramolecular approach to design a promising class of multifunctional nanoparticles based on molecular recognition of nucleobases, which combine excellent tumor-targeting capability via aptamer, controlled drug release, and efficient fluorescent imaging for cancer-specific therapy. First, an amphiphilic prodrug dioleoyl clofarabine was self-assembled into micellar nanoparticles with hydrophilic nucleoside analogue clofarabine on their surface. Thereafter, two types of single-stranded DNAs that contain the aptamer motif and fluorescent probe Cy5.5, respectively, were introduced onto the surface of the nanoparticles via molecular recognition between the clofarabine and the thymine on DNA. These drug-containing multifunctional nanoparticles exhibit good capabilities of targeted clofarabine delivery to the tumor site and intracellular controlled drug release, leading to a robust and effective antitumor effect in vivo.

DNA Trojan Horses: Self‐Assembled Floxuridine‐Containing DNA Polyhedra for Cancer Therapy

Based on their structural similarity to natural nucleobases, nucleoside analogue therapeutics were integrated into DNA strands through conventional solid-phase synthesis. By elaborately designing their sequences, floxuridine-integrated DNA strands were synthesized and self-assembled into well-defined DNA polyhedra with definite drug-loading ratios as well as tunable size and morphology. As a novel drug delivery system, these drug-containing DNA polyhedra could ideally mimic the Trojan Horse to deliver chemotherapeutics into tumor cells and fight against cancer. Both in vitro and in vivo results demonstrate that the DNA Trojan horse with buckyball architecture exhibits superior anticancer capability over the free drug and other formulations. With precise control over the drug-loading ratio and structure of the nanocarriers, the DNA Trojan horse may play an important role in anticancer treatment and exhibit great potential in translational nanomedicine.

Biotic and abiotic molecule dopants determining the electrochemical performance, stability and fibroblast behavior of conducting polymer for tissue interface

Because the growth activities of cells considerably depend on the surface characteristics of tissue culture substrates, tissue–substrate interface is a crucial factor in modulating the behavior of cells in tissue engineering. Conducting polymers with excellent biocompatibility act as ideal tissue interface material because they can be facilely fabricated into multiple structures, patterned to undergo electrical stimulation and modified with different dopants. Meanwhile, the performance of conducting polymers is significantly influenced by the characteristics of negatively charged dopants. Herein, six kinds of biotic and abiotic molecules with electronegative groups are used as counterions to dope poly(3,4-ethylenedioxythiophene) (PEDOT). A comprehensive evaluation of the properties of PEDOT, including electrochemistry, electrical stimulation, stability and biocompatibility is provided for further comparison and analysis. This work would reinforce our understanding of the dopant-dependent performance of conducting polymers for tissue engineering and applications in electrophysiological recording and stimulation.

Flexible intramuscular micro tube electrode combining electrical and chemical interface

With the rapidly developed micromachining technology, various kinds of sophisticated microelectrodes integrated with micro fluidic channels are design and fabricated for not only electrophysiological recording and stimulation, but also chemical drug delivery. As many efforts have been devoted to develop rigid microprobes for neural research of brain, few researchers concentrate on fabrication of flexible microelectrodes for intramuscular electrophysiology and chemical interfacing. Since crude wire electrodes still prevail in functional electrical stimulation (FES) and electromyography (EMG) recording of muscle, here we introduce a flexible micro tube electrode combining electrical and chemical pathway. The proposed micro tube electrode is manufactured based on polymer capillary, which provide circumferential electrode site contacting with electro-active tissue and is easy to manufactured with low cost.

Molecular insights for the biological interactions between polyethylene glycol and cells

As the gold standard polymer for drug delivery system, polyethylene glycol (PEG) has excellent biocompatibility. Its reported that the low nonspecific interactions between PEG and body contribute to its biocompatibility. However, here we discover dynamic biological interactions exist between PEG and cells on the molecular level. PEG (2 kD) can induce metabolism modulations and survival autophagy by creating an intracellular hypoxic environment, which act as cellular survival strategies in response to the hypoxia. In the cellular adaption process during hypoxia, PEG-treated cells decrease energy consumption by reducing cell growth rate, increase energy supply by amino acid catabolism in a short period, and survival autophagy over a relatively long period, to keep energy homeostasis and survival. Our research provides molecular insights for understanding the mechanism underlying the excellent biocompatibility of PEG, which will be of fundamental importance for further related studies on other polymers and development of polymeric materials with improved characteristics.

Hydrogen Peroxide-Responsive Nanoprobe Assists Circulating Tumor Cell Identification and Colorectal Cancer Diagnosis

In the clinic, numeration of circulating tumor cells (CTCs) plays a critical role in cancer diagnosis and treatment, but conventional CTC identification and counting that rely on specific antibodies to characterize a cells surface antigens are costive and with limitations. Importantly, false positive or negative results may occur due to the high heterogeneity and epithelial-mesenchymal transition (EMT) of CTCs. Herein we demonstrate a novel and effective CTC detecting nanoprobe that could rapidly respond to the high level of endogenous H2O2 of CTCs and report the signal through fluorescence emission. Briefly, a hydrophobic coumarin-benzene boronic acid pinacol ester (Cou-Bpin) was grafted onto hydrophilic glycol chitosan (GC) to form an amphiphilic molecule, which further assembled into micellar nanoparticles in aqueous solution. This new nanoprobe was highly sensitive to H2O2 with a detection limit of 0.1 μM and could rapidly enter the cells within 30 min. Upon exposure to intracellular H2O2, the nanoprobe exhibited remarkable one-photon and two-photon luminescent characteristics, which were suitable for imaging of endogenous H2O2 of various human colorectal cancer cells and assist the identification of CTCs. Compared to a conventional CTC counting assay, the nanoprobe-based CTC numeration could overcome the false-negative findings due to the low expression of cytokeratin 19 (CK19). In a clinic test, CTC counting results based on the new nanoprobe match better to the postoperative pathological results of four clinic patients who had colorectal cancer at different stages.

Poly(3,4-ethylenedioxythiophene)/graphene oxide composite coating for electrode-tissue interface

Owing to interacting with the living tissue directly, the electrode-tissue interface largely determines the performance of the whole bioelectronics devices. The miniaturization of biomedical electronic components requires interface materials to possess properties including excellent electrical performance, good biocompatibility and compatibility with microelectronic fabrication process. Considering the unique characteristics and wide applications in biomedical domain of conducting polymer and graphene, composite film consists of poly(3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) is proposed as electrode-tissue interface in this work. The facilely electrochemically synthesized PEDOT/GO coating on microelectrodes shows low impedance, high charge storage capacity and good biocompatibility to act as electrode-tissue interface. As a result, the composite film is a potential biomaterial as electrode-tissue interface for tissue engineering and further implantable electrophysiological devices.

Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy

A combinatorial therapy that utilizes two or more therapeutic modalities is more effective in overcoming the limitations than each individual method used alone. Despite great advances have been achieved, the combination of chemotherapy and photodynamic therapy (PDT) still cannot satisfy the clinic requirements as the antitumor efficacy could be severely affected by tumor-associated hypoxia. Herein, for the first time, we reported a platinum(IV) complex-based polyprodrug that can in situ generate the highly toxic platinum(II) species as chemotherapeutics and simultaneously induce a high level of reactive oxygen species (ROS) in a PDT-like process without the use of photosensitizer and consumption of oxygen. By in situ polymerizing the platinum(IV) complex-based prodrug monomer (PPM) and 2-methacryloyloxy ethyl phosphorylcholine (MPC), nanosized hydrogel-like polyprodrug could be synthesized. Upon being exposed to light, Pt(IV) moieties in this photoactivable polyprodrug were reduced to generate Pt(II) species. At the meantime, a high level of ROS was generated without the presence of endogenous oxygen, which was confirmed by electron spin resonance (ESR) and fluorescence probes. With the unique nanosized architecture and photoresponsive feature, the as-synthesized polyprodrug exhibited the advantages of sustained drug release, long-term circulation, preferable tumor accumulation, and reversing drug resistance by downregulating the expression of multidrug resistance-associated protein 1 (MRP1) in the anticancer treatment.